Title of Invention	A METHOD FOR MANUFACTURING A SHAPE BODY CONTAINING A STARCH
Abstract	The present invention relates to a process for the production of a starch containing shaped body, in particular a soft capsule with single part capsule shell, characterized by the following steps. A) conversion of a mixture comprising at least one native or chemically modified starch with an amylopectin content of greater than or equal to 50% by weight, based on the weight of the anhydrous starch, water, and at least one organic plasticizer, where the content of organic plasticizer is in the range from 37% by weight to 50% by weight, based on the weight of the anhydrous starch, with melting and kneading, into a homogenized, thermo plastic molten composition in a first processing apparatus; b) production of at least one extrudate, in particular of an extruded film, at the exit from the first processing apparatus, c) forming of the extrudate to give a shaped body in a continuous or intermittent forming process; where the steps a) and b) are carried out in such a way7 that in step c) the value of the Staudinger index of the composition forming the extrudate is at least 40 ml/g, preferably at least 50 ml/g and more preferably at least 60 ml/g.

Title of Invention

A METHOD FOR MANUFACTURING A SHAPE BODY CONTAINING A STARCH

Abstract

The present invention relates to a process for the production of a starch containing shaped body, in particular a soft capsule with single part capsule shell, characterized by the following steps. A) conversion of a mixture comprising at least one native or chemically modified starch with an amylopectin content of greater than or equal to 50% by weight, based on the weight of the anhydrous starch, water, and at least one organic plasticizer, where the content of organic plasticizer is in the range from 37% by weight to 50% by weight, based on the weight of the anhydrous starch, with melting and kneading, into a homogenized, thermo plastic molten composition in a first processing apparatus; b) production of at least one extrudate, in particular of an extruded film, at the exit from the first processing apparatus, c) forming of the extrudate to give a shaped body in a continuous or intermittent forming process; where the steps a) and b) are carried out in such a way7 that in step c) the value of the Staudinger index of the composition forming the extrudate is at least 40 ml/g, preferably at least 50 ml/g and more preferably at least 60 ml/g.

Full Text	A method for manufacturing a shape body containing a starch, a homogenised mass containing starch and a device for manufactur¬ing a soft capsule The invention relates to a method for manufacturing a shape body containing a starch, a homogenised mass containing starch and a device for manufacturing a soft capsule according to the pream¬bles of the independent claims. Shape bodies from biodegradable materials for reasons of envi¬ronmental protection have been of extraordinary interest for a long time. As a result of the problems with BSE in particular capsules with a capsule casing of gelatin-free materials have been gaining importance for the administration of pharmaceutically effective substances. In a series of publications the manufacture of insert capsules from starch are described, such as in EP 118 240 and US 4,738,724. The insert capsules are premanufactured as a two-part casing with the injection moulding method, where appropriate af¬ter intermediate storage filled with highly viscous or solid ac¬tive substances. On account on unsealedness of the insert con¬nection, insert capsules are not suitable for low viscous flu¬ids. Furthermore the manufacturing process of a filled insert capsule is complicated and expensive since the working steps of manufacture and filling the capsule casing must be carried out separate from one another. For fluid, in the broadest sense pumpable capsule content mate¬rials, capsules with a one-part capsule casing of gelatin have proven themselves and these may be manufactured in continuous automatisable methods. The manufacture of the capsule casing and the filling of this at the same time is effected in a single working step. In this continuous, 1-step method shape parts are manufactured from which the capsule casing during and after the filling are joined together by welding the outer edges of the shape parts. The shape part manufacture is effected either by way of diverging and converging moulds, such as with the Norton, Banner or Schering process or by way of rotating shaping drums, as is e.g. realised in the rotary die process and in the Accogel method ("Die Kapsel" Fahrig/Hofer - Publisher, Stuttgart 1983; Lachmann/Liebermann/Kanig, "The Theory and Practice of Indus¬trial Pharmacy"; Third Edition, Philadelphia 1986). The filling is effected with the help of metering pumps which deliver a de¬fined quantity of active substance during the punching out and welding of the shape parts for forming a one-piece capsule cas¬ing. The welding, i.e. the forming of the seams is effected gen¬erally by way of pressure and heat. The manufacturing costs are considerably reduced with respect to two-part insert capsules. US 5,342,626 describes the manufacture of capsules in the rotary die process, wherein the capsule casing material consists of carrageen, mannan gums, such as e.g. galactomannans and gluco-mannans, gelan or mixtures amongst one another. These macromo-lecular vegetable biopolymers are however not acceptable with respect to cost since the raw materials are too expensive. The manufacturing process for one-part capsules sets a series of demands on the capsule casing material. One of the main precon¬ditions is the capability of the capsule casing material to form highly elastic "endless" tapes with a sufficient strength. The capsule casing must when required dissolve rapidly in the stom¬ach and intestinal tract in order to be able to release the ac¬tive substances. The capsule casing material must be weldable. The molecules of the material forming the shape parts, in par¬ticular the macromolecules of the polymer should at the location of the seam ideally penetrate in order to ensure a sufficient stability of the seam location. Gelatine fullfills all these conditions in an almost ideal manner and until now could not be replaced as a material for one-part capsules. Under the criteria of availablility and cost, starch for the manufacture of one-part capsule casings is also a desirable ini¬tial material. The manufacture of starch films has already been described sev¬eral times, the combination of properties which such a starch film must have for manufacturing one-part capsules has not been disclosed up to now. EP 474 705 describes a method for manufacturing starch shape bodies by extrusion of a starch molten mass. The starch molten mass contains starch with an amylose content over 50% and addi¬tives. From the molten mass, before, during and/or after the ex¬truding, the water is removed by applying a vacuum. The foils extruded from this material have an elongation at rupture be¬tween 80 and 200%. Starches with a high amylose content are not suitable as capsule casing materials since the tendency of the amylose chains to retrograde stands in the way of a quick dis¬solving of the capsule casing. EP 0 397 819 discloses a method for manufacturing thermoplasti-cally processable starch, wherein the crystalline part in the starch lies below 5%. The method consists of mixing native starch with at least 10% by weight of an additives which has a solubility parameter of at least 3 0.7 (MPa)^^^. The mixture is conveyed into a molten mass by heating at a temperature between 120"C and 2200. The water content of the starch already is re¬duced to below 5% in the molten mass. The molar mass of the ap- plied starch before conveying into the thermoplastic condition is larger than 1,000,000 Daltons, preferably between 3,000,000 Daltons and 10,000,000 Daltons. Although this method yields a thermoplastic starch with a good workability into shape bodies which have a sufficient strength, the elongation at rupture of the shape bodies manufactured with this thermoplastic starch only reaches values between 40 and 55%. The elasticity of the starch film is thus too low for the manufacture of one-part cap¬sule casings in a continuous method and leads to a tearing of the shape parts on manufacture or to a tearing of the finished capsule. The starch film does not have the weldability or seam¬ing strength which are sufficient for the demands which are made on one-part capsule casings. EP 304 401 likewise describes a method for manufacturing shaped objects from starch. The thermoplastic starch molten mass re¬quired for this is manufactured from a pre-treated starch. The destructurisation {destruction of the crystalline region) of the native starch and the subsequent homogenisation {conveying into the thermoplastic condition) in each case takes place at tem¬peratures between 120°C and 190°C in a closed vessel with a wa¬ter content between 10 and 20%. The elongation at rupture of starch films manufactured according to this method is not suffi¬cient for the production of one-part capsule casings in a con¬tinuous method. The starch films show furthermore also an insuf¬ficient weldability and seam strength. EP 0 542 155 discloses biodegradable shaping masses which amongst other things are suitable for the manufacture of film. The shaping masses apart from thermoplastically processable starches contain cellulose derivatives. The elongation at rup¬ture does not exceed the value of 85% which is not sufficient for the manufacture of one-part capsule casings in a continuous method. The weldability of the films is unsatisfactory. Many of the polymer blends disclosed in EP 542 155 contain substances which are not allowed for pharmaceutical application or for foodstuffs. WO 97/35537 discloses one-part capsules manufactured by way of rotating shaping drums and containing jellied starch. The part etching of the film surface has shown to be disadvantageous for the manufacture of one-part capsules with respect to the trans¬port and pressure stability {on pressing the capsules out of the blister packages). By way of this the capsule casings at the re¬gion of the seam location become too soft and flexible. The object of the present invention is to overcome the problems of the state of the art. In particular the object of the present invention is to provide a gelatine-free shape body and a method for its manufacture. In particular starch capsules with a one-part capsule casing shall be provided. A further object is to provide a starch containing film which by way of semi-continuous or continuous method, in particular by way of the rotary die process, may be processed to one-part cap¬sule casings. Still a further object is to provide a starch film for manufac¬turing a capsule casing, which with the prevailing processing conditions during the encapsulation proceedings has an elonga¬tion at rupture of at least 100% Still a further object is Co provide a starch films with a good weldability. still a further object is to provide starch capsules with a one-part capsule casing which after a storage duration of at least one year neither exhibit unsealedness, nor changes in the dis¬solving speed of the capsule casing. These objects are solved by the features of the independent claims. In particular they are solved by a method for manufacturing a starch containing shape body, in particular a soft capsule with a one-part capsule casing, wherein the method comprises the steps of a) processing a mixture containing at least one starch, water, and at least one organic softener, whilst heating and knead¬ing, into a thermoplastically processable, preferably ho¬mogenised mass in a first processing device; b) where appropriate manufacturing an storable intermediate product, in particular a granulate after cooling of the mass obtained in step a) and subsequent heating the intermediate product into a thermoplastically processable mass in a sec¬ond processing device; c) manufacturing at least one material line, in particular an extruded film, at the exit of the first or where appropriate second processing device; d) re-shaping the material line into a shape body in a continu¬ous or intermittent shaping method; e) where appropriate drying the shape body. wherein the steps a) to c) are carried out in a manner such that in step d) the limiting viscosity number [TI] (Staudinger Index) of the starch in the mass forming the material line has a value of not less than 40 ml/g,, preferably of at least 50 ml/g and even more preferred of at least 80 ml/g. Even better properties are obtained when the limiting viscosity number of the starch has a value of equal or more than 100 ml/g. The most advanta¬geous properties are obtained with a value of the limiting vis¬cosity number of the starch of more than or equal to 13 0 ml/g. The limiting viscosity number may not exceed a maximal value of 1000 ml/g. In an advantageous embodiment the limiting viscosity number does not exceed 700 ral/g and even more preferred 300 ml/g. The mixture applied in step a) contains a starch preferably in a weight range of 45 to 80% by weight with respect to the total weight of the mixture. The term "one-part" is to be understood as a differentiation with respect to two-part capsules which are produced by way of inserting and/or adhesing of two capsule parts with outer edges lying over one another. The one-part capsule casing may com¬pletely be without a seam location or when it is formed from shape parts may be formed with a welded seam location. The term „soft capsule" is to be understood as a product of the commonly used continuous and semi-continuous, 1-step manufac¬turing methods for producing one-part capsules as cited in the literature. The term does not serve so much as a differentiation of the softener content since also hard capsules, (as a descrip¬tion for joined together two-part capsules), may contain a sof¬tener content of up to 12% with respect to the total mass. The terms "thermoplastically processable, melt and amorphous" are defined according to Rompp Chemie Lexikon, publisher: J. Falbe, M. Regitz, 9^^ Edition, 1992, Georg Thieme publishing house, Stuttgart. The term starch is to be understood as native starches as well as physically and/or chemically modified starches. According to the invention all starches independent of the plant which it is extracted are suitable for the mixture used in step a) of the method. In a preferred embodiment form the starch has an amylo-pectine content above 50% with respect to the total weight of the water-free starch. Physically and/or chemically modified po¬tato starches have shown to be preferred for the method. For the present invention however in the broadest sense all polyglucans, i.e. 1,4 and/or 1,6 poly-a-D-glucans and/or mix¬tures between these are suitable. In a preferred embodiment the starch is a hydroxypropylated starch. The degree of substitution (DS) is in the region of 0.01 to 0.5, preferably in the region of 0.05 to 0.25 and even more preferred in the region of 0.1 to 0.15. Particularly preferred is hydroxypropylated potato starch. In a further preferred embodiment the starch is a pasted gelati¬nized, pre-cooked starch. Above a temperature typical for each type of starch "dissolving" i.e. irreversible desintegration of the starch grains in aqueous starch suspensions occurs after the reaching the highest degree of swelling. This procedure is called "gelatinisation". The gelatinisation, i.e. the irreversi¬ble swelling of the starch grain at a high temperature of up to 40 times the original volume involves a gradual uptake of water and dissolving of hydrogen bridge bonds which permits a further hydration up to the complete desintegration of the starch gran¬ule structure. The processing of the starch containing mixture into the thermo-plastically processable, preferably homogenised condition in step a) just as the subsequently following processing steps b) and c) must be effected under conditions which prevent an uncon¬trolled breakdown of the amylose molecules and amylopectine molecules to short fragments. The cooperation of all processing parameters such as e.g. tem¬perature, pressure, sojourn time and kneading power must be taken into account during steps a) to c) in order to prevent an extensive breakdown of the starch molecules. Thus e.g. also at relatively high temperatures an extensive breakdown of the starch molecules may be avoided when the sojourn times of the starch containing mass" are kept small at these temperatures. In a preferred embodiment the temperature of the thermoplasti-cally processable mass in the first and where appropriate second processing device, as well as on manufacture of the material line does not exceed 160°C, preferably not 120°C and even more preferred not 90°C. At 160°C also the desintegration procedure in step a) is completed in less than 5 minutes, preferably less than 3 minutes. In a further preferred embodiment the energy transferred to the mass by kneading on producing the homogenised mass in the steps a) to c) does not exceed 0.3 kWh/kg, preferably 0.2 kWh/kg and even more preferred 0.175 kWh/kg. The processing into the thermoplastically processable condition effects an irreversible swelling of the starch grains, which is a precondition for the mass to be able to be processed into the homogeneous condition and to remain homogenised after the cool¬ing . By way of the steps a) to c) there is produced a mass in which there are essentially no longer present any crystalline regions in the starch. Crystalline regions in the extruded material line lead to the formation of pinholes, i.e. to inhomogenities in the material which then have a particularly disadvantageous effect when the material line in step c) is an extruded film. "Essen¬tially no longer present any crystalline regions" is to mean that these are destroyed so much that a worsening of the physi¬cal parameters of the extruded material, which are relevant to the re-shaping, may not be led back to the presence of crystal¬line regions. The term „homogeneous mass/material" and „homogenised mate¬rial/mass" is to be understood as a material or mass which at every location in the material has essentially the same physical properties/parameters. Slight deviations may occur on the re¬spective material or shape part surface by way of the uptake of air humidity. In the context of the present invention a mass is homogeneous or homogenised when under the microscope the number of the still visible starch grains lies below one percent in av¬erage. For this the mass in the thermoplastically processable condition is cooled down, cut into thin slices and analysed un¬der the light microscope. A homogenised mass is obtained by processing the mixture to a softened or even liquid condition resulting in a thermoplasti¬cally processable condition. The major part of the components making the mixture (starch, organic softener, lubricating and release agent) can be present in a molten starch and with a suf- ficiently long standing or mixing Ocneading) duration the compo¬sition is essentially the same at every location of the mass {homogeneous mass). This homogeneous condition is kept also with and after the cooling of the thermoplastic condition. Essen¬tially no demixing processes occur. This ensures uniform me¬chanical properties of the shape body at room temperature. The limiting viscosity number [T)] or also (Staudinger Index) within a polymeric homologous row has the following relation to the molar mass and the weight average of the molecular weight distribution [TI] = K X M° wherein a is an exponent dependent on the molecule shape and the K-value a constant dependent on the dissolved substance and on the solvent. The limiting viscosity number within a polymeric homologous row is larger the larger is the molecular weight of the polymer with otherwise unchanged parameters. The measurement of the limiting viscosity number is not able to give the abso¬lute molecular weights. The evaluation of absolute molecular masses of starches is as known extremely difficult and the result is dependent on the ap¬plied measuring method. This applies even more the more branched the molecules are. Thus, also the results of the absolute mo¬lecular mass measurement of amylopectine and amylopectine-containing starches have a high degree of uncertainty. Since the absolute molecular mass measurement is furthermore very expen¬sive, the measurement of the limiting viscosity number gives quicker, more reliable values which are more adapted for the purpose. without delivering an exhaustive explanation it is assumed that first of all the polymerisation degree of the amylopectine mole¬cules of the applied starch is shown to be responsible for the elasticity of the material line produced in step d). A high elongation at rupture is of great importance, in particular for a web-like film which is to be shaped in the rotary die method into a soft capsule. There exists the idea that additionally to the inherent elastic¬ity of the starch gels, which with a sufficient polymerisation degree of the being constituent part of the starch amylopectin molecules is given anyway, there may also arise a type of „starch network" which is built up by entwining and entanglement of the amylopectine molecules and which is supported by the branchings of the molecules. But also amylose molecules may with a sufficiently high degree of polymersisation participate in these „starch networks". Also the chemical substitution of the starch hydroxyl groups under formations of ether, ester, vinyl and acetal bondings may be advantageous since they encourage the formation of the "starch networks". Step d) and step e) are effected under conditions which prevent a further breakdown of the amylose and amylopectine molecules. The shape body obtained in step d) or e) with this has essen¬tially the same degree of polymerisation of the starch which the steps a) to c) have effected. The presence of these networks and possibly also the presence of analytically non-provable nanocrystals which are not visible in the form of pinhole formation (analogous to soft PVC} is appar¬ently responsible for the occurence of an elastic plateau. Young"s modulus of elasticity E of amorphous non cross-linked polymers and in particular of linear polymers normally falls al- most linearly down to 0°C with an increasing temperature after running through the region of the glass transition temperature. The polymers behave as a liquid by sufficiently high tempera¬ture. The characteristics of an elastic plateau in contrast is that the mechanical properties such as Young"s modulus of elas¬ticity E, the elongation at rupture Eb, the maximal strength an,, etc. over a longer temperature range remain approximately con¬stant and almost independent of the temperature. An elastic pla¬teau is normaly only to be observed with cross-linked (chemical cross-linking) polymers (cf. Introduction to Polymers, Publ. R. J. Young, P. A. Lovell, Chapman and Hall, London, 2"^ edition 1991, page 344/345). Unexpectedly the masses of the present in¬vention inspite of the absence of chemical cross-linking have an elastic plateau. Against this background there may also be understood the advan¬tageous properties of a 1,4 and 1,6 polyglucan which is co-crystallised with short linear chains of 1,4 polyglucans. By way of the co-crystallisation on the one hand there arise further branchings which act positively on the formation of a network and on the other hand there arise non-visible nano-crystalline regions. Preferably as 1,4 and 1,6 polyglucans there are applied amylopectines. The masses according to the invention and the masses obtained with the manufacturing method according to the invention show in the temperature range from about 20°C to approx. 80°C mechanical properties, such as 8b, dm* E which are essentially independent of the temperature. The elastic plateau for the reshaping and filling of the films into filled shape bodies is of decisive im¬portance. Thus Young"s modulus of elasticity E of the starch containing film according to the invention is at the moment of reshaping and filling in the rotary die process is maximal 2MPa, preferred maximal 1 MPa. In other words, given the contact pres¬sure of the filling wedge of the machine, the film may not coun¬ter with such a resistance to the filling pressure of the fill¬ing material which finally effect the shaping-out of the capsule casing in the rotary die process that filling material runs out between the film and the filling wedge. It is indeed the tem¬perature independence of £b and am between 40""C and 90""C which permits the processability of the films manufactured from these masses into soft capsules with the rotary die method. The re-shaping procedure of the material line into a shape body, in particular the re-forming of an extruded film into a one-part soft capsule with the method known in the technology demands extensions at rupture of the material line, in particu¬lar of the film, of at least 100% in the range of between 40°C and 90°C, preferably of between 60°C to 80°C. In a preferred em¬bodiment the elongation at rupture of the material line, in par¬ticular the film is at least 150% and even more preferred at least 240%. The strength a^ of the material line, in particular of the shape body manufactured therefrom at 25°C and 60% relative air humid¬ity must be at least 2 MPa. In a preferred embodiment a^ is larger or equal to 3.5 MPa and even more preferred larger than or equal to 5 MPa. This value ensures at room temperature a suf¬ficient stability of the capsule casing {packaging, storing, transport safety and use). The filling is however effected at an increased temperature of the film which renders a filling pressure of no more than 2 MPa necessary . This is given with a Young"s modulus of elasticity E of smaller than or equal to 2MPa at the encapsulation tempera- ture (40^0 to 90°C) with the present masa. This has already been explained with the citations on the elastic plateau. The total softener content of the mixture applied in step a) is at least 12% by weight with respect to the weight of the water-free starch. In a preferred embodiment the content of the sof¬tener is in a region of 30% by weight to 60% by weight and even more preferred in a region of 38% by weight to 55% by weight. By way of leading the process according to the invention one succeeds in the extensive exclusion of heavily broken-down oli-gomeres of the starch. This permits high overall quantities of softeners to be worked into the mass. The oligomeres arising with the homogenising methods of the state of the art would likewise display a softening effect and the working-in of large quantities of softners would not be possible. Preferably those softeners are applied which have solubility pa¬rameters equal to or more than 16.3 (MPa)^^^. The organic soften¬ers are selected from the group consisting of polyalcohols, or¬ganic acids, amines, acid amides and sulphoxides. Preferred are polyalcohols. However also water functions as a softener and thus forms a part of the total softener content. The water con¬tent of the mixture applied in step a) lies in a region of 6 to 3 0% by weight with respect to the total mixture. The water constituent part of the mixture applied in step a) may in the method according to the invention be changed in step b) or c) in a directed manner. The physical parameters which are dependent on the water content may therefore be subject to changes. To the mixture applied in step a) yet be added at least one ad¬ditive in a weight range of 3.5% by weight to 15% by weight, preferably from 5% by weight to 8% by weight with respect to the total weight of the mixture in order to comply with the required properties of the shape body resulting in d) and e) there may The additives are selected from the group consisting of carbon¬ates and/or hydrogen carbonates of alkali ions or alkaline earth ions, further disintegration agents, colourings, preservatives, antioxidants, physically and/or chemically modified biopolymers, in particular polysaccharides and vegetable polypeptides. The opacity of the homogenised mass is e.g. achieved preferably with the addition of titanium dioxide as a filler. As a disintegration agent, for a quick disintegration of the capsule casing preferably calcium carbonate and amylases are added. The group of the physically and/or chemically modified bio¬polymers comprises cellulose, in particular part hydroxypro-pylated cellulose, alginate, carageenan, galactomannans, gluco-mannans, casein. In a preferred embodiment the mixture applied in step a) addi¬tionally comprises an internal lubricant and release agent, which is selected from the group consisting of lecithins, mono-glycerides, diglycerides and triglycerides of edible fatty ac¬ids, polyglycerine ester of edible fatty acids, polyethylene glycol ester of edible fatty acids, sugar ester of edible fatty acids and edible fatty acids. The lubricant and release agent is contained in the mixture in a region of 0 to 4% by weight with respect to the total weight of the mixture. Preferably it is added to the mixture in 0.5 to 2% by weight and. even more preferred in 0.8 to 1.5% by weight. Ad¬vantageously the lubricant and release agent is selected from the group consisting of glycerine monostearate and lecithin. Edible fatty acids are to be understood as the monocarbon acids occuring as acid components of the triglycerides of natural fats. They have an even number of C-atoms and have an unbranched carbon skeleton. The chain length of the fatty acids varies from 2 to 26 C-atoms. A large group of the fatty acids are unsatu¬rated fatty acids. The starch mass in the thermoplastically processable condition in step c) may be extruded by way of wide-slot nozzles into a starch film or starch tape. The mass however can also be cooled unformed from the thermoplastic condition, cooled, dried and processed into a storable granulate (with the sealing from mois¬ture} . This granulate is available for a later processing. Op¬tionally to the mass processed to granulates there may be added only a part of the necessary lubricant and release agent, sof¬tener and additives. One may e.g. renounce to the addition of animal and/or vegetable fats for avoiding undesired colour ef¬fects in the first processing means and only admix these laters on remelting the granulate in the second processing device. The extruded tapes are then either directly processed further or where appropriate are wound onto rolls for storage, using plas¬tic foils as an intermediate layer. Polyethylene has been shown to be a suitable foil material. The starch film obtained by the method according to the inven¬tion may be particularly processed into soft capsules on all in¬stallations known from the state of the art for manufacturing one-part capsules. Continuous installations and in particular the rotary die process have shown to be suitable. The capsule wall is welded under the effect of heat preferably larger or equal to SCC from two shape part halves which have previously been punched from a starch film. Two "endless starch films" are led through two neighbouring rollers or drums having reliefs, these rollers or drums rotating in opposing directions. Whilst the starch film by way of the filling pressure of the filling mass is pressed into the relief and thus the capsule halves are formed, the pumpable or injectable capsule filling is exactly metered by way of a valve and via a filling wedge is introduced into the entry let-in of the shaping drums. The shape and size of the capsule is thus dependent on the geometric dimensions of the reliefs in the drums and the metered filling volume. To be consistent the term capsule is thus not only to be under¬stood as the typical capsule shape, but also every other form of "casing" such as e.g. balls, cushions and figures. Until today there exist numerous further developments and deviations from this basic principle. The one-part capsule casings manufactured by way of the starch film according to the invention may be additionally coated, e.g. in order to delay the release of active substances. The coextrusion, coating and laminating of the starch film ac¬cording to the invention with materials whose film-forming prop¬erty is based on synthetic and/or natural polymers creates addi¬tional possibilities of forming certain properties of the cap¬sule casing by way of a multi-layer foil. In particular by way of the multi-layer construction a starch foil may be manufactured which on the inner side has an easily weldable coating whilst the outer side is coated in a manner such that a delayed effect of the breakdown of the capsule sets in. Part of the present invention is therefore further a homogenised starch containing mass which comprises at least one essentially amorphous starch preferably present in a weight range of 45 to 80% by weight with respect to the total weight of the mass, the mass comprises further water, at least one organic softener in a constituent part of at least 12% by weight with respect to the weight of the water-free starch, wherein the limiting viscosity number of the starch in the homogenised mass is at least 40 ml/g. Preferably the limiting viscosity number of the starch is at least 50 ml/g, even more preferred at least 80 ml/g. Particu¬larly preferred is a limiting viscosity number of the starch of larger than or equal to 100 ml/g. Even better properties are obtained with a limiting viscosity number of the starch of larger than or equal to 130 ml/g. The limiting viscosity number of the starch may not exceed 1000 ml/g, preferably 700 ml/g and even more preferred 300 ml/g. Advantageously a starch with an amylopectine content of larger than or equal to 50% by weight with respect to the weight of the water-free starch is applied The content of organic softeners lies advantageously in the range of 30% by weight to 60% by weight and even more preferred in a range of 3 8 to 55% by weight and even more preferred in a range of between 40 to 50% by weight with respect to the total weight of the mass. with respect to the embodiments of the softener, starch and ad¬ditives, the corresponding embodiments"for the method are re¬ferred to. In a particular embodiment the shape body has a water content of maximal 15% by weight with respect to the total weight of the mass. If the mass is formed as a film and is to be used for the manu¬facture of one-part capsule casings with the rotary die process, an elongation at rupture at an encapsulation temperature of 40°C to 90 °C of at least 100% is required, preferably the elongation at rupture however lies at at least 160% and even more preferred at least 240%. The shape body, in particular the soft capsule casing formed from the film has at 25°C and 60% relative air humidity a strength a^ of preferably at least 3.5 MPa and even more pre¬ferred at least 5 MPa. Part of the invention are further shape bodies which are manu¬factured from the mass according to the invention. Furthermore part of the invention is a one-part capsule casing which contains starch with a limiting viscosity number of at least 40 ml/g, preferably of at least 50 ml/g and even more pre¬ferred of at least 80 ml/g. Particularly advantageous is a cap¬sule with a limiting viscosity number of the starch of lOo ml/g and even better a limiting viscosity number of 130 ml/g. The masses according to the invention are well suitable for the manufacture of multi-chamber especially two-chamber capsules as they are for example described in WO 00/28976. There occur al- most now stresses since the water content of the film or films may be set low, in the finished dried capsules, in particular in the separating walls forming the chambers. This considerably in¬crease the stability of the multi-chamber capsule in comparison to multi-chamber soft gelatine capsules. For example two-chamber capsules may be realised whose one cham¬ber is filled with a powder or granulate and whose other chamber contains a liquid. The shape body, in particular the capsule casing has a thickness in the region between 0.1 and 2 mm, preferably between 0.2 and 0.6 mm. In a further preferred embodiment the shape body, in particular the soft gelatine capsule consists of a multi-layered film. At least two of the films have a differing chemical composition. Disregarding the manufacture of one-layered capsule casings the thermoplastically processable starch molten mass may also be used for manufacturing any other type of shape body, in particu¬lar packaging materials. In the thermoplastic condition the mass may be worked, in particular extruded. One example of the invention in an aspect with regard to the de¬vice is represented in the figures and is hereinafter explained in more detail. There are shown in Figure 1 the elongation at rupture [sb] of the mass according to the invention containing starch, in dependence on the limiting viscosity number [q], Figure 2 a heavily schematised representation of a filling and shaping station in the rotary die method and Figure 3 the symbolic representation of a double screw-type ex¬truder with the temperature conditions prevailing therein. Figure 4 shows Young"s modulus of elasticity E [MPa] of a ho¬mogenised mass containing a starch according to the in¬vention, in dependence on the temperature (conditioned 50% relative humidity). The measurement of the elongation at rupture and Young"s modulus of elasticity E is performed according to DIN Standard 53455 re¬spectively DIN EN ISO 527-1 to ISO 527-3. The measurement of the elongation at rupture is performed according to this DIN stan¬dard at the corresponding encapsulation temperature. The measurement of the limiting viscosity number [nJ is per¬formed analogously to the DIN Standard: DIN 51562-1 to 51562-4. However the softener content of the samples and its influence on the run-through times in the Ubbelohde vicosity meter now had to be taken into account. For this firstly the influence of the softener content on the run-through time to was determined, by way of the obtained calibration lines then the run-through times tosoftener could be Calculated with any softener content according to tosoftener = t o " ( 1 ■ 0 0 0 02 + 0 . 0 02 3 8 - Cgoftener) wherein Caoftener is the concentration of softener present, in mg/ml. The limiting viscosity number determined for Che broken down starches together with the mechanical properties of the as¬sociated samples are set up in Table 1. The manufacture of the samples which in Figure 1 demonstrates the connection between the elongation at rupture and the limit¬ing viscosity number, is effected in the following manner starch: 56.2 to 56.9% by weight glycerine: 41.8% by weight with respect to the content of the water-free starch water: 1,3 - 2.0% by weight with respect to the total weight of the mixture. The mixtures were homogenised in a Brabender kneader at 160 rpm with a kneading time of in each case 15 min and at variable kneading temperatures of llCC, 160""C, 200=0, 220°C and 235°C. Figure 1 shows the dependency of the elongation at rupture of the mass containing starch on the limiting viscosity number of the starch. From Figure 1 and the associated Table 1 it is evi¬dent that with an increasing temperature in the Brabender kneader the limiting viscosity number of the starch reduces, i.e. with an otherwise unchanged composition and unchanged proc¬ess parameters (only variable is the temperature) the degree of breakdown of the starch increases. 97% elongation at rupture is reached at a limiting viscosity number of 82.8 ml/g. Thereafter the elongation at rupture with an increasing value of the limit¬ing viscosity number runs asymptotically to a limit value of ap-prox. 105%. The initial value of the limiting viscosity number, i.e. the value from which a noticeable rise of the elongation at rupture is observed is independent on the softener constituent part and singly dependent on the molecular weight average of the starch molecules or the corresponding limiting viscosity number. with a lower content of softener the shape of the graph flattens i.e. the graph is shifted to lower values of the elongation of rupture. Even when the limiting viscosity number of the whole mass is measured, the value of the number is essentially dependent on the polymerisation degree of the starch. The value of the limit¬ing viscosity number is essentially independent of the remaining components of the mass (or their low influence may mathemati¬cally be taken into account). The maximal strength a^ was evaluated analogously to DIN standard 53455 and DIN EN ISO 527-1 to ISO 527-3. Also a^, exhibits a de¬pendency on the limiting viscosity number, i.e. the degree of breakdown of the starch. The lower the limiting viscosity number with otherwise unchanged conditions is, the lower is c^. The filling and shaping station indicated as a whole at 1 in Figure 2 comprises for the encapsulation a shaping drum pair 6, 6", wherein in the surface of the shaping drums there are ar¬ranged the recesses necessary for shaping the capsules. In the entry let-in of the shaping drum pair there is arranged a fill¬ing wedge 5 through which by way of a delivery pump 5 the fill¬ing material may be introduced. With the present embodiment ex¬ample the capsule casing consists of two layers with different material properties which are formed by the two starch films 7a, 7a" on the one hand and 7b, 7b" on the other hand. These two starch films are prepared in the worm-type extruders 2a, 2a" and 2b, 2b" and via diverting drums 3, directly and with the same conveying speed, are led to the entry let-in of the shaping drum pair 6, 6". The worm-type extruders are with this arranged next to the filling and shaping station and where appropriate ar¬ranged on the same machine frame. The starch films are between the shaping drum pair shaped and welded into a one-part soft capsule, wherein they enclose the filling material. The individual capsules 9 are collected and in any case led to a drying process whilst the remaining film skeleton 8 possibly by recycling is again processed to new cap¬sules . The direct arrangement of the extruder next to the shaping and filling station and the „inline" supply of the extruding film into the shaping and filling station (without intermediate stor¬age) is of course possible at any time, thus also with the manu¬facture of single-layered capsule casings (usual rotary die method). Figure 3 shows in a heavily simplified manner a double worm-type extruder 10 which in the present case is composed of twelve in¬dividual housing blocks 1 -12. The housing blocks are continu¬ously numbered from left to right. Each housing block may be electrically heated with a separate control circuit and/or be cooled with valve-controlled influxes with cold water. Further¬more individual blocks may be provided with connection pieces as will yet be explained hereinafter. In the present case it is the case of equally rotating, tightly meshing double worm-type ex¬truders, wherein the diameter of a worm is 44 mm. The length of the whole worm shaft is 2,112 mm, which corresponds to a ratio of length to diameter of 48. At the end of the extruder the ma¬terial is delivered via a nozzle 14. This nozzle may for example comprise twelve hole bores of 2 mm diameter. At the same time it would be conceivable for the manufacture of the granulate to hot-sprue the individual material lines and then lead them to a fluid bed dryer. At the nozzle 14 however also directly a fin¬ished material film may be removed. On the worms 12 at suitable locations there are arranged knead¬ing disks 13 of differing configurations in order to achieve as homogeneous as possible kneading of the material mixture. The block 1 is cooled with water and provided with a powder feed 15. The block 2 is closed whilst on block 3 there is arranged an in¬jection nozzle 16 for a fluid metering into the kneading space. In the transition region of the blocks 2 and 3 there are ar¬ranged fine neutral kneading disks 13. The blocks 4 to 6 are again closed, wherein on block 5 there are provided broad, neu¬tral and back-conveying kneading disks. Block 7 has at its dis¬posal a connection conduit 17 which is connected to a vacuum source. On block 8 again there is arranged a powder feed 18 and the worm is provided with a fine, neutral and/or conveying kneading disk. Block 9 likewise has at its disposal an injection nozzle 19 whilst block 10 is closed. The worm in block 10 in contrast has at its disposal broad, neutral and back-conveying kneading disks. Block 11 has a further connection conduit 20 which may be connected to a vacuum source or to the atmosphere. Block 12 is closed, the worm here however has medium, conveying kneading disks. Below the schematic conveying worm there is drawn up a tempera¬ture curve. The adjustable temperature accuracy is +/- 3°C. With the specified temperatures it is the case of the block tempera¬ture which does not compellingly need to be identical to the temperature in the molten mass. The temperature in the molten mass is evidently still influenced by other parameters, in par¬ticular by the rotational speed of the worm. With the extrusion it is therefore necessary to take account of these conditions and to match the adjustable variables to one another such that optimal material properties are achieved. With the embodiment example described by way of this Figure a rotational speed of 340 revolutions per minute (rpm) is made. The total throughput is approx. 34.3 kg/h and the energy uptake approx. 0.175 kWh/kg. To the block 1 held at 20°C there is me¬tered 20 kg/hour (approx. 60%) of starch powder. The powder is entered with shifting edges and then supplied to the blocks 2 and 3 heated to 100°C. With block 3 there is effected a metering of 11 kg/h {approx. 3 0%) glycerine with a working pressure of at least 10 bar via a gravimetric piston pump. In the closed blocks 4 to 6 the temperature is increased to 140°G. With block 7 there is applied a vaccum of 800 mbar, wherein approx. 6% water exits. The temperature is now again taken back to 110°C. With block 8 there is effected a supply of 1.4 kg/h {approx 10%) of calcium carbonate. Where appropriate at block 9 1.9 kg/h {approx. 5 to 8%) of glycerine may be metered. The working pressure is like¬wise at least 10 bar. If this connection is not required it is closed with a blind plug. At block 11 again there is applied a vacuum, wherein approx. 2 to 4% water exits. Where appropriate an atmospheric aeration is also sufficient. The temperature of the molten mass may at no location of the ex¬truder exceed 160*"C since otherwise a thermal breakdown of the starch sets in. Furthermore it is the case that the thermal change of the starch is smaller, the shorter the molten mass is subjected to a higher temperature. Therefore an optimal relation between temperture control and material throughput must be cre¬ated. In Figure 4 there is shown the temperature dependence of Young"s modulus of elasticity E. The composition of the test samples corresponds to Example 2 {unbroken line). In comparison thereto the theoretical temperature behaviour of a thermoplast of a similar glass transition temperature is represented. Whilst the modulus of elasticity of the „normal" thermoplast (dashed line) falls rapidly linearly to zero, with the test samples the modulus of elasticity in a region of 40°C to approx. 70°C is al¬most independent of the temperature. This behaviour is amongst other things also responsible for the advantageous properties of the present invention The present invention is further explained by way of the subse¬quent examp1e s: Example 1 Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition: starch: 7.7 kg/h lecithin: 0.147 kg/h glycerine monostearate: 0.147 kg/h glycerine (99.5 purity): 4.47 kg/h calcium carbonate, precipitated: 1.0 kg/h wherein with a worm rotational speed of 180 rpm one extruded un¬der the following conditions (see Figure 3): block 1: 25°C block 2 and 3 100°C block 4 to 6 140°C block 7 to 9: llCC block 10 to 12: 110°C nozzle: 110°C With respect to the water-free starch this corresponds to a glycerine content of 38.77%, With respect to the water-free end product there resulted the following constituent parts: lecithin: 1.11% glycerine-raonostearate 1.11% starch (water-free): 55.15% CaCOa: 7.76% glycerine: 34.87% Specific energy uptake on extrusion: 0.275 kWh/kg The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [ri] of the starch in the starch containing mass is 107,2 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 102% +/-10%. Example 2 Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition: starch: 7.7 kg/h lecithin: 0.147 kg/h glycerine monostearate: 0.147 kg/h glycerine (99.5 purity): 4.67 kg/h Wherein with a worm rotational speed of 260 rpm one extruded un¬der the same conditions as in Example 1. In block 4 alternatively a vacuum may be applied in order to re¬move excess water (from the starch powder) (e.g. 800 mbar). With respect to the water-free starch this corresponds to a glycerine content of 39.81%. With respect to the water-free end product there resulted the following constituent parts: lecithin: 1.18% glycerine monostearate 1.18% starch (water-free): 58.81% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [r\] of the starch in the starch containing mass is 115,6 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 107% +/-10%. Exan^le 3 Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition: All details in % by weight starch: 57.88% lecithin: 1.06% glycerine monostearate: 1.06% glycerine (98% purity): 3.64% sorbitol syrup (containing 30% water) 36.36% wherein one produces under the following parameters worm rotational speed of the two shaft extruder = 150 r.p.m. Into the blocks 7 and 10 via a vacuum pump there was applied a pressure of 400 mbar in order to remove excess water {which amongst other things is introduced into the product via the moisture content of the starch and of the sorbitol syrup). Block temperatures block 1: block 2 and 3: block 4 & 5 block 6 & 7 block 8 & 9 block 10-12 nozzle: 20°C iio°c: 140°C 120""C 110°C lOO^C 95°C The specific energy uptake on extrusion was 0.195 kWh/kg With respect to the water-free end product there results the following composition (all details in percentage by weight): starch (water-free): lecithin: 61.25% 1.31% glycerine-monostearate: 1.32% glycerine: 4.44% sorbitol: 31.69% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [ri] of the starch in the starch containing mass is 92,5 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 107% +/- 10%. Example 4 Extrusion conditions as in Example 3 and the following dosages: Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition: All details in % by weight starch: glycerine monostearate: glycerine (98% purity): sorbitol syrup {containing 30% water): 58 .92% 1 .08% 3 .64% 36. 36% The specific energy uptake on extrusion was 0.265 kWh/)cg With respect to the water-free end product there results the following composition (all details in percentage by weight): starch (water-free): 62.46% glycerine-monostearate: 1,35% glycerine: 4.44% sorbitol: 31.75% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [T\] of the starch in the starch containing mass is 126,3 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 156% +/-10%. Example 5 Extrusion conditions as in Example 3 and the following dosages: Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously and processed to a thermoplastically processable condition: All details in % by weight. starch: 62.95% glycerine monostearate: 1.15% glycerine (98% purity): 8.28% sorbitol (30% water content) 27.61% The specific energy uptake on extrusion was 0.295 kWh/kg With respect to the water-free end product there results the following composition (all details in percentage by weight): starch (water-free): 65.17% glycerine-monostearate: 1.40% glycerine: 9.89% sorbitol: 23.54% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [T\] of the starch in the starch containing mass is 79,3 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 203% +/■ 10%. Example 6 Extrusion conditions as in Example 3 and the following dosages: Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition: All details in % by weight starch: 55.80% glycerine monostearate: 1.02% glycerine (98% purity): 3.93% sorbitol sirup (containing 30% water): 19.63% maltitol syrup (containing 25% water): 19.63% The specific energy uptake on extrusion was 0.225 kWh/kg With respect to the water-free end product there results the following composition (all details in percentage by weight): starch (water-free): 58.73% glycerine-monostearate 1.26% glycerine: 4.76% sorbitol: 17.01% raaltitol: 18.23% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [r\] of the starch in the starch containing mass is 74,8 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 184% +/-10%. Example 7 Extrusion conditions as in Example 3 and the following dosages: Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition: All details in % by weight starch: 59.88% glycerine monostearate: 1.10% glycerine (98% purity): 3.55% sorbitol sirup (with a high constituent part of hydrated oligosaccharides): 17.74% sorbitol (containing 30% water) 17.74% The specific energy uptake on extrusion was 0.185 kWh/kg With respect to the water-free end product there results the following composition (all details in percentage by weight): starch (water-free): 63.36% glycerine-monostearate 1.37% glycerine: 4.33% sorbitol: 15.46% sorbitol with a high constituent part of hydrated oligosaccharides: 15.46% The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process. The limiting viscosity number [r]] of the starch in the starch containing mass is 88,1 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 240% +/-10%. Tab.l The mechanical properties of the starch film with 41.8% glycerine in dependence on the limiting viscos¬ity number [TIJ °C H2O % [tl] ml/g d mm CTTH MP a % 110 1.77 160.5 0.72 7.0 +/- 0.3 107 +•/- 6 14 0 1.80 139.9 0.65 6.8 +/- 0.4 106 +/- 18 160 1.55 127.9 0.64 6.3 +/- 0.4 99 +/- 5 180 1.54 115.6 0.64 6.9 +/- 0.2 107 +/- 9 220 1.66 82.8 0.73 4.8 +/- 0.4 97 +/- 23 200 1.55 59.2 0.61 4.9 +/- 0.5 69 +/- 23 235 1.30 51.5 0.87 9.0 +/- 0.7 22 +/- 24

Full Text

A method for manufacturing a shape body containing a starch, a homogenised mass containing starch and a device for manufactur¬ing a soft capsule
The invention relates to a method for manufacturing a shape body containing a starch, a homogenised mass containing starch and a device for manufacturing a soft capsule according to the pream¬bles of the independent claims.
Shape bodies from biodegradable materials for reasons of envi¬ronmental protection have been of extraordinary interest for a long time. As a result of the problems with BSE in particular capsules with a capsule casing of gelatin-free materials have been gaining importance for the administration of pharmaceutically effective substances.
In a series of publications the manufacture of insert capsules from starch are described, such as in EP 118 240 and US 4,738,724. The insert capsules are premanufactured as a two-part casing with the injection moulding method, where appropriate af¬ter intermediate storage filled with highly viscous or solid ac¬tive substances. On account on unsealedness of the insert con¬nection, insert capsules are not suitable for low viscous flu¬ids. Furthermore the manufacturing process of a filled insert capsule is complicated and expensive since the working steps of manufacture and filling the capsule casing must be carried out separate from one another.
For fluid, in the broadest sense pumpable capsule content mate¬rials, capsules with a one-part capsule casing of gelatin have proven themselves and these may be manufactured in continuous automatisable methods. The manufacture of the capsule casing and the filling of this at the same time is effected in a single

working step. In this continuous, 1-step method shape parts are manufactured from which the capsule casing during and after the filling are joined together by welding the outer edges of the shape parts. The shape part manufacture is effected either by way of diverging and converging moulds, such as with the Norton, Banner or Schering process or by way of rotating shaping drums, as is e.g. realised in the rotary die process and in the Accogel method ("Die Kapsel" Fahrig/Hofer - Publisher, Stuttgart 1983; Lachmann/Liebermann/Kanig, "The Theory and Practice of Indus¬trial Pharmacy"; Third Edition, Philadelphia 1986). The filling is effected with the help of metering pumps which deliver a de¬fined quantity of active substance during the punching out and welding of the shape parts for forming a one-piece capsule cas¬ing. The welding, i.e. the forming of the seams is effected gen¬erally by way of pressure and heat. The manufacturing costs are considerably reduced with respect to two-part insert capsules.
US 5,342,626 describes the manufacture of capsules in the rotary die process, wherein the capsule casing material consists of carrageen, mannan gums, such as e.g. galactomannans and gluco-mannans, gelan or mixtures amongst one another. These macromo-lecular vegetable biopolymers are however not acceptable with respect to cost since the raw materials are too expensive.
The manufacturing process for one-part capsules sets a series of demands on the capsule casing material. One of the main precon¬ditions is the capability of the capsule casing material to form highly elastic "endless" tapes with a sufficient strength. The capsule casing must when required dissolve rapidly in the stom¬ach and intestinal tract in order to be able to release the ac¬tive substances. The capsule casing material must be weldable. The molecules of the material forming the shape parts, in par¬ticular the macromolecules of the polymer should at the location

of the seam ideally penetrate in order to ensure a sufficient stability of the seam location. Gelatine fullfills all these conditions in an almost ideal manner and until now could not be replaced as a material for one-part capsules.
Under the criteria of availablility and cost, starch for the manufacture of one-part capsule casings is also a desirable ini¬tial material.
The manufacture of starch films has already been described sev¬eral times, the combination of properties which such a starch film must have for manufacturing one-part capsules has not been disclosed up to now.
EP 474 705 describes a method for manufacturing starch shape bodies by extrusion of a starch molten mass. The starch molten mass contains starch with an amylose content over 50% and addi¬tives. From the molten mass, before, during and/or after the ex¬truding, the water is removed by applying a vacuum. The foils extruded from this material have an elongation at rupture be¬tween 80 and 200%. Starches with a high amylose content are not suitable as capsule casing materials since the tendency of the amylose chains to retrograde stands in the way of a quick dis¬solving of the capsule casing.
EP 0 397 819 discloses a method for manufacturing thermoplasti-cally processable starch, wherein the crystalline part in the starch lies below 5%. The method consists of mixing native starch with at least 10% by weight of an additives which has a solubility parameter of at least 3 0.7 (MPa)^^^. The mixture is conveyed into a molten mass by heating at a temperature between 120"C and 220*0. The water content of the starch already is re¬duced to below 5% in the molten mass. The molar mass of the ap-

plied starch before conveying into the thermoplastic condition is larger than 1,000,000 Daltons, preferably between 3,000,000 Daltons and 10,000,000 Daltons. Although this method yields a thermoplastic starch with a good workability into shape bodies which have a sufficient strength, the elongation at rupture of the shape bodies manufactured with this thermoplastic starch only reaches values between 40 and 55%. The elasticity of the starch film is thus too low for the manufacture of one-part cap¬sule casings in a continuous method and leads to a tearing of the shape parts on manufacture or to a tearing of the finished capsule. The starch film does not have the weldability or seam¬ing strength which are sufficient for the demands which are made on one-part capsule casings.
EP 304 401 likewise describes a method for manufacturing shaped objects from starch. The thermoplastic starch molten mass re¬quired for this is manufactured from a pre-treated starch. The destructurisation {destruction of the crystalline region) of the native starch and the subsequent homogenisation {conveying into the thermoplastic condition) in each case takes place at tem¬peratures between 120°C and 190°C in a closed vessel with a wa¬ter content between 10 and 20%. The elongation at rupture of starch films manufactured according to this method is not suffi¬cient for the production of one-part capsule casings in a con¬tinuous method. The starch films show furthermore also an insuf¬ficient weldability and seam strength.
EP 0 542 155 discloses biodegradable shaping masses which amongst other things are suitable for the manufacture of film. The shaping masses apart from thermoplastically processable starches contain cellulose derivatives. The elongation at rup¬ture does not exceed the value of 85% which is not sufficient for the manufacture of one-part capsule casings in a continuous

method. The weldability of the films is unsatisfactory. Many of the polymer blends disclosed in EP 542 155 contain substances which are not allowed for pharmaceutical application or for foodstuffs.
WO 97/35537 discloses one-part capsules manufactured by way of rotating shaping drums and containing jellied starch. The part etching of the film surface has shown to be disadvantageous for the manufacture of one-part capsules with respect to the trans¬port and pressure stability {on pressing the capsules out of the blister packages). By way of this the capsule casings at the re¬gion of the seam location become too soft and flexible.
The object of the present invention is to overcome the problems of the state of the art.
In particular the object of the present invention is to provide a gelatine-free shape body and a method for its manufacture. In particular starch capsules with a one-part capsule casing shall be provided.
A further object is to provide a starch containing film which by way of semi-continuous or continuous method, in particular by way of the rotary die process, may be processed to one-part cap¬sule casings.
Still a further object is to provide a starch film for manufac¬turing a capsule casing, which with the prevailing processing conditions during the encapsulation proceedings has an elonga¬tion at rupture of at least 100%
Still a further object is Co provide a starch films with a good weldability.

still a further object is to provide starch capsules with a one-part capsule casing which after a storage duration of at least one year neither exhibit unsealedness, nor changes in the dis¬solving speed of the capsule casing.
These objects are solved by the features of the independent claims.
In particular they are solved by a method for manufacturing a
starch containing shape body, in particular a soft capsule with
a one-part capsule casing, wherein the method comprises the
steps of
a) processing a mixture containing at least one starch, water, and at least one organic softener, whilst heating and knead¬ing, into a thermoplastically processable, preferably ho¬mogenised mass in a first processing device;
b) where appropriate manufacturing an storable intermediate product, in particular a granulate after cooling of the mass obtained in step a) and subsequent heating the intermediate product into a thermoplastically processable mass in a sec¬ond processing device;
c) manufacturing at least one material line, in particular an extruded film, at the exit of the first or where appropriate second processing device;
d) re-shaping the material line into a shape body in a continu¬ous or intermittent shaping method;
e) where appropriate drying the shape body.

wherein the steps a) to c) are carried out in a manner such that in step d) the limiting viscosity number [TI] (Staudinger Index) of the starch in the mass forming the material line has a value of not less than 40 ml/g,, preferably of at least 50 ml/g and even more preferred of at least 80 ml/g. Even better properties are obtained when the limiting viscosity number of the starch has a value of equal or more than 100 ml/g. The most advanta¬geous properties are obtained with a value of the limiting vis¬cosity number of the starch of more than or equal to 13 0 ml/g. The limiting viscosity number may not exceed a maximal value of 1000 ml/g. In an advantageous embodiment the limiting viscosity number does not exceed 700 ral/g and even more preferred 300 ml/g.
The mixture applied in step a) contains a starch preferably in a weight range of 45 to 80% by weight with respect to the total weight of the mixture.
The term "one-part" is to be understood as a differentiation with respect to two-part capsules which are produced by way of inserting and/or adhesing of two capsule parts with outer edges lying over one another. The one-part capsule casing may com¬pletely be without a seam location or when it is formed from shape parts may be formed with a welded seam location.
The term „soft capsule" is to be understood as a product of the commonly used continuous and semi-continuous, 1-step manufac¬turing methods for producing one-part capsules as cited in the literature. The term does not serve so much as a differentiation of the softener content since also hard capsules, (as a descrip¬tion for joined together two-part capsules), may contain a sof¬tener content of up to 12% with respect to the total mass.

The terms "thermoplastically processable, melt and amorphous" are defined according to Rompp Chemie Lexikon, publisher: J. Falbe, M. Regitz, 9*^*^ Edition, 1992, Georg Thieme publishing house, Stuttgart.
The term starch is to be understood as native starches as well as physically and/or chemically modified starches. According to the invention all starches independent of the plant which it is extracted are suitable for the mixture used in step a) of the method. In a preferred embodiment form the starch has an amylo-pectine content above 50% with respect to the total weight of the water-free starch. Physically and/or chemically modified po¬tato starches have shown to be preferred for the method.
For the present invention however in the broadest sense all polyglucans, i.e. 1,4 and/or 1,6 poly-a-D-glucans and/or mix¬tures between these are suitable.
In a preferred embodiment the starch is a hydroxypropylated starch. The degree of substitution (DS) is in the region of 0.01 to 0.5, preferably in the region of 0.05 to 0.25 and even more preferred in the region of 0.1 to 0.15. Particularly preferred is hydroxypropylated potato starch.
In a further preferred embodiment the starch is a pasted gelati¬nized, pre-cooked starch. Above a temperature typical for each type of starch "dissolving" i.e. irreversible desintegration of the starch grains in aqueous starch suspensions occurs after the reaching the highest degree of swelling. This procedure is called "gelatinisation". The gelatinisation, i.e. the irreversi¬ble swelling of the starch grain at a high temperature of up to 40 times the original volume involves a gradual uptake of water and dissolving of hydrogen bridge bonds which permits a further

hydration up to the complete desintegration of the starch gran¬ule structure.
The processing of the starch containing mixture into the thermo-plastically processable, preferably homogenised condition in step a) just as the subsequently following processing steps b) and c) must be effected under conditions which prevent an uncon¬trolled breakdown of the amylose molecules and amylopectine molecules to short fragments.
The cooperation of all processing parameters such as e.g. tem¬perature, pressure, sojourn time and kneading power must be taken into account during steps a) to c) in order to prevent an extensive breakdown of the starch molecules. Thus e.g. also at relatively high temperatures an extensive breakdown of the starch molecules may be avoided when the sojourn times of the starch containing mass" are kept small at these temperatures.
In a preferred embodiment the temperature of the thermoplasti-cally processable mass in the first and where appropriate second processing device, as well as on manufacture of the material line does not exceed 160°C, preferably not 120°C and even more preferred not 90°C. At 160°C also the desintegration procedure in step a) is completed in less than 5 minutes, preferably less than 3 minutes.
In a further preferred embodiment the energy transferred to the mass by kneading on producing the homogenised mass in the steps a) to c) does not exceed 0.3 kWh/kg, preferably 0.2 kWh/kg and even more preferred 0.175 kWh/kg.
The processing into the thermoplastically processable condition effects an irreversible swelling of the starch grains, which is

a precondition for the mass to be able to be processed into the homogeneous condition and to remain homogenised after the cool¬ing .
By way of the steps a) to c) there is produced a mass in which there are essentially no longer present any crystalline regions in the starch. Crystalline regions in the extruded material line lead to the formation of pinholes, i.e. to inhomogenities in the material which then have a particularly disadvantageous effect when the material line in step c) is an extruded film. "Essen¬tially no longer present any crystalline regions" is to mean that these are destroyed so much that a worsening of the physi¬cal parameters of the extruded material, which are relevant to the re-shaping, may not be led back to the presence of crystal¬line regions.
The term „homogeneous mass/material" and „homogenised mate¬rial/mass" is to be understood as a material or mass which at every location in the material has essentially the same physical properties/parameters. Slight deviations may occur on the re¬spective material or shape part surface by way of the uptake of air humidity. In the context of the present invention a mass is homogeneous or homogenised when under the microscope the number of the still visible starch grains lies below one percent in av¬erage. For this the mass in the thermoplastically processable condition is cooled down, cut into thin slices and analysed un¬der the light microscope.
A homogenised mass is obtained by processing the mixture to a softened or even liquid condition resulting in a thermoplasti¬cally processable condition. The major part of the components making the mixture (starch, organic softener, lubricating and release agent) can be present in a molten starch and with a suf-

ficiently long standing or mixing Ocneading) duration the compo¬sition is essentially the same at every location of the mass {homogeneous mass). This homogeneous condition is kept also with and after the cooling of the thermoplastic condition. Essen¬tially no demixing processes occur. This ensures uniform me¬chanical properties of the shape body at room temperature.
The limiting viscosity number [T)] or also (Staudinger Index) within a polymeric homologous row has the following relation to the molar mass and the weight average of the molecular weight distribution
[TI] = K X M°
wherein a is an exponent dependent on the molecule shape and the K-value a constant dependent on the dissolved substance and on the solvent. The limiting viscosity number within a polymeric homologous row is larger the larger is the molecular weight of the polymer with otherwise unchanged parameters. The measurement of the limiting viscosity number is not able to give the abso¬lute molecular weights.
The evaluation of absolute molecular masses of starches is as known extremely difficult and the result is dependent on the ap¬plied measuring method. This applies even more the more branched the molecules are. Thus, also the results of the absolute mo¬lecular mass measurement of amylopectine and amylopectine-containing starches have a high degree of uncertainty. Since the absolute molecular mass measurement is furthermore very expen¬sive, the measurement of the limiting viscosity number gives quicker, more reliable values which are more adapted for the purpose.

without delivering an exhaustive explanation it is assumed that first of all the polymerisation degree of the amylopectine mole¬cules of the applied starch is shown to be responsible for the elasticity of the material line produced in step d). A high elongation at rupture is of great importance, in particular for a web-like film which is to be shaped in the rotary die method into a soft capsule.
There exists the idea that additionally to the inherent elastic¬ity of the starch gels, which with a sufficient polymerisation degree of the being constituent part of the starch amylopectin molecules is given anyway, there may also arise a type of „starch network" which is built up by entwining and entanglement of the amylopectine molecules and which is supported by the branchings of the molecules. But also amylose molecules may with a sufficiently high degree of polymersisation participate in these „starch networks". Also the chemical substitution of the starch hydroxyl groups under formations of ether, ester, vinyl and acetal bondings may be advantageous since they encourage the formation of the "starch networks".
Step d) and step e) are effected under conditions which prevent a further breakdown of the amylose and amylopectine molecules. The shape body obtained in step d) or e) with this has essen¬tially the same degree of polymerisation of the starch which the steps a) to c) have effected.
The presence of these networks and possibly also the presence of analytically non-provable nanocrystals which are not visible in the form of pinhole formation (analogous to soft PVC} is appar¬ently responsible for the occurence of an elastic plateau. Young"s modulus of elasticity E of amorphous non cross-linked polymers and in particular of linear polymers normally falls al-

most linearly down to 0°C with an increasing temperature after running through the region of the glass transition temperature. The polymers behave as a liquid by sufficiently high tempera¬ture. The characteristics of an elastic plateau in contrast is that the mechanical properties such as Young"s modulus of elas¬ticity E, the elongation at rupture Eb, the maximal strength an,, etc. over a longer temperature range remain approximately con¬stant and almost independent of the temperature. An elastic pla¬teau is normaly only to be observed with cross-linked (chemical cross-linking) polymers (cf. Introduction to Polymers, Publ. R. J. Young, P. A. Lovell, Chapman and Hall, London, 2"*^ edition 1991, page 344/345). Unexpectedly the masses of the present in¬vention inspite of the absence of chemical cross-linking have an elastic plateau.
Against this background there may also be understood the advan¬tageous properties of a 1,4 and 1,6 polyglucan which is co-crystallised with short linear chains of 1,4 polyglucans. By way of the co-crystallisation on the one hand there arise further branchings which act positively on the formation of a network and on the other hand there arise non-visible nano-crystalline regions. Preferably as 1,4 and 1,6 polyglucans there are applied amylopectines.
The masses according to the invention and the masses obtained with the manufacturing method according to the invention show in the temperature range from about 20°C to approx. 80°C mechanical properties, such as 8b, dm* E which are essentially independent of the temperature. The elastic plateau for the reshaping and filling of the films into filled shape bodies is of decisive im¬portance. Thus Young"s modulus of elasticity E of the starch containing film according to the invention is at the moment of reshaping and filling in the rotary die process is maximal 2MPa,

preferred maximal 1 MPa. In other words, given the contact pres¬sure of the filling wedge of the machine, the film may not coun¬ter with such a resistance to the filling pressure of the fill¬ing material which finally effect the shaping-out of the capsule casing in the rotary die process that filling material runs out between the film and the filling wedge. It is indeed the tem¬perature independence of £b and am between 40""C and 90""C which permits the processability of the films manufactured from these masses into soft capsules with the rotary die method.
The re-shaping procedure of the material line into a shape body, in particular the re-forming of an extruded film into a one-part soft capsule with the method known in the technology demands extensions at rupture of the material line, in particu¬lar of the film, of at least 100% in the range of between 40°C and 90°C, preferably of between 60°C to 80°C. In a preferred em¬bodiment the elongation at rupture of the material line, in par¬ticular the film is at least 150% and even more preferred at least 240%.
The strength a^ of the material line, in particular of the shape body manufactured therefrom at 25°C and 60% relative air humid¬ity must be at least 2 MPa. In a preferred embodiment a^ is larger or equal to 3.5 MPa and even more preferred larger than or equal to 5 MPa. This value ensures at room temperature a suf¬ficient stability of the capsule casing {packaging, storing, transport safety and use).
The filling is however effected at an increased temperature of the film which renders a filling pressure of no more than 2 MPa necessary . This is given with a Young"s modulus of elasticity E of smaller than or equal to 2MPa at the encapsulation tempera-

ture (40^0 to 90°C) with the present masa. This has already been explained with the citations on the elastic plateau.
The total softener content of the mixture applied in step a) is at least 12% by weight with respect to the weight of the water-free starch. In a preferred embodiment the content of the sof¬tener is in a region of 30% by weight to 60% by weight and even more preferred in a region of 38% by weight to 55% by weight.
By way of leading the process according to the invention one succeeds in the extensive exclusion of heavily broken-down oli-gomeres of the starch. This permits high overall quantities of softeners to be worked into the mass. The oligomeres arising with the homogenising methods of the state of the art would likewise display a softening effect and the working-in of large quantities of softners would not be possible.
Preferably those softeners are applied which have solubility pa¬rameters equal to or more than 16.3 (MPa)^^^. The organic soften¬ers are selected from the group consisting of polyalcohols, or¬ganic acids, amines, acid amides and sulphoxides. Preferred are polyalcohols. However also water functions as a softener and thus forms a part of the total softener content. The water con¬tent of the mixture applied in step a) lies in a region of 6 to 3 0% by weight with respect to the total mixture.
The water constituent part of the mixture applied in step a) may in the method according to the invention be changed in step b) or c) in a directed manner. The physical parameters which are dependent on the water content may therefore be subject to changes.

To the mixture applied in step a) yet be added at least one ad¬ditive in a weight range of 3.5% by weight to 15% by weight, preferably from 5% by weight to 8% by weight with respect to the total weight of the mixture in order to comply with the required properties of the shape body resulting in d) and e) there may The additives are selected from the group consisting of carbon¬ates and/or hydrogen carbonates of alkali ions or alkaline earth ions, further disintegration agents, colourings, preservatives, antioxidants, physically and/or chemically modified biopolymers, in particular polysaccharides and vegetable polypeptides.
The opacity of the homogenised mass is e.g. achieved preferably with the addition of titanium dioxide as a filler.
As a disintegration agent, for a quick disintegration of the capsule casing preferably calcium carbonate and amylases are added.
The group of the physically and/or chemically modified bio¬polymers comprises cellulose, in particular part hydroxypro-pylated cellulose, alginate, carageenan, galactomannans, gluco-mannans, casein.
In a preferred embodiment the mixture applied in step a) addi¬tionally comprises an internal lubricant and release agent, which is selected from the group consisting of lecithins, mono-glycerides, diglycerides and triglycerides of edible fatty ac¬ids, polyglycerine ester of edible fatty acids, polyethylene glycol ester of edible fatty acids, sugar ester of edible fatty acids and edible fatty acids.
The lubricant and release agent is contained in the mixture in a region of 0 to 4% by weight with respect to the total weight of

the mixture. Preferably it is added to the mixture in 0.5 to 2% by weight and. even more preferred in 0.8 to 1.5% by weight. Ad¬vantageously the lubricant and release agent is selected from the group consisting of glycerine monostearate and lecithin.
Edible fatty acids are to be understood as the monocarbon acids occuring as acid components of the triglycerides of natural fats. They have an even number of C-atoms and have an unbranched carbon skeleton. The chain length of the fatty acids varies from 2 to 26 C-atoms. A large group of the fatty acids are unsatu¬rated fatty acids.
The starch mass in the thermoplastically processable condition in step c) may be extruded by way of wide-slot nozzles into a starch film or starch tape. The mass however can also be cooled unformed from the thermoplastic condition, cooled, dried and processed into a storable granulate (with the sealing from mois¬ture} . This granulate is available for a later processing. Op¬tionally to the mass processed to granulates there may be added only a part of the necessary lubricant and release agent, sof¬tener and additives. One may e.g. renounce to the addition of animal and/or vegetable fats for avoiding undesired colour ef¬fects in the first processing means and only admix these laters on remelting the granulate in the second processing device.
The extruded tapes are then either directly processed further or where appropriate are wound onto rolls for storage, using plas¬tic foils as an intermediate layer. Polyethylene has been shown to be a suitable foil material.
The starch film obtained by the method according to the inven¬tion may be particularly processed into soft capsules on all in¬stallations known from the state of the art for manufacturing

one-part capsules. Continuous installations and in particular the rotary die process have shown to be suitable. The capsule wall is welded under the effect of heat preferably larger or equal to SCC from two shape part halves which have previously been punched from a starch film. Two "endless starch films" are led through two neighbouring rollers or drums having reliefs, these rollers or drums rotating in opposing directions. Whilst the starch film by way of the filling pressure of the filling mass is pressed into the relief and thus the capsule halves are formed, the pumpable or injectable capsule filling is exactly metered by way of a valve and via a filling wedge is introduced into the entry let-in of the shaping drums. The shape and size of the capsule is thus dependent on the geometric dimensions of the reliefs in the drums and the metered filling volume.
To be consistent the term capsule is thus not only to be under¬stood as the typical capsule shape, but also every other form of "casing" such as e.g. balls, cushions and figures. Until today there exist numerous further developments and deviations from this basic principle.
The one-part capsule casings manufactured by way of the starch film according to the invention may be additionally coated, e.g. in order to delay the release of active substances.
The coextrusion, coating and laminating of the starch film ac¬cording to the invention with materials whose film-forming prop¬erty is based on synthetic and/or natural polymers creates addi¬tional possibilities of forming certain properties of the cap¬sule casing by way of a multi-layer foil.
In particular by way of the multi-layer construction a starch foil may be manufactured which on the inner side has an easily

weldable coating whilst the outer side is coated in a manner such that a delayed effect of the breakdown of the capsule sets in.
Part of the present invention is therefore further a homogenised starch containing mass which comprises at least one essentially amorphous starch preferably present in a weight range of 45 to 80% by weight with respect to the total weight of the mass, the mass comprises further water, at least one organic softener in a constituent part of at least 12% by weight with respect to the weight of the water-free starch, wherein the limiting viscosity number of the starch in the homogenised mass is at least 40 ml/g.
Preferably the limiting viscosity number of the starch is at least 50 ml/g, even more preferred at least 80 ml/g. Particu¬larly preferred is a limiting viscosity number of the starch of larger than or equal to 100 ml/g. Even better properties are obtained with a limiting viscosity number of the starch of larger than or equal to 130 ml/g. The limiting viscosity number of the starch may not exceed 1000 ml/g, preferably 700 ml/g and even more preferred 300 ml/g.
Advantageously a starch with an amylopectine content of larger than or equal to 50% by weight with respect to the weight of the water-free starch is applied
The content of organic softeners lies advantageously in the range of 30% by weight to 60% by weight and even more preferred in a range of 3 8 to 55% by weight and even more preferred in a range of between 40 to 50% by weight with respect to the total weight of the mass.

with respect to the embodiments of the softener, starch and ad¬ditives, the corresponding embodiments"for the method are re¬ferred to.
In a particular embodiment the shape body has a water content of maximal 15% by weight with respect to the total weight of the mass.
If the mass is formed as a film and is to be used for the manu¬facture of one-part capsule casings with the rotary die process, an elongation at rupture at an encapsulation temperature of 40°C to 90 °C of at least 100% is required, preferably the elongation at rupture however lies at at least 160% and even more preferred at least 240%.
The shape body, in particular the soft capsule casing formed from the film has at 25°C and 60% relative air humidity a
strength a^ of preferably at least 3.5 MPa and even more pre¬ferred at least 5 MPa.
Part of the invention are further shape bodies which are manu¬factured from the mass according to the invention.
Furthermore part of the invention is a one-part capsule casing which contains starch with a limiting viscosity number of at least 40 ml/g, preferably of at least 50 ml/g and even more pre¬ferred of at least 80 ml/g. Particularly advantageous is a cap¬sule with a limiting viscosity number of the starch of lOo ml/g and even better a limiting viscosity number of 130 ml/g.
The masses according to the invention are well suitable for the manufacture of multi-chamber especially two-chamber capsules as they are for example described in WO 00/28976. There occur al-

most now stresses since the water content of the film or films may be set low, in the finished dried capsules, in particular in the separating walls forming the chambers. This considerably in¬crease the stability of the multi-chamber capsule in comparison to multi-chamber soft gelatine capsules.
For example two-chamber capsules may be realised whose one cham¬ber is filled with a powder or granulate and whose other chamber contains a liquid.
The shape body, in particular the capsule casing has a thickness in the region between 0.1 and 2 mm, preferably between 0.2 and 0.6 mm.
In a further preferred embodiment the shape body, in particular the soft gelatine capsule consists of a multi-layered film. At least two of the films have a differing chemical composition.
Disregarding the manufacture of one-layered capsule casings the thermoplastically processable starch molten mass may also be used for manufacturing any other type of shape body, in particu¬lar packaging materials. In the thermoplastic condition the mass may be worked, in particular extruded.
One example of the invention in an aspect with regard to the de¬vice is represented in the figures and is hereinafter explained in more detail. There are shown in
Figure 1 the elongation at rupture [sb] of the mass according to the invention containing starch, in dependence on the limiting viscosity number [q],

Figure 2 a heavily schematised representation of a filling and shaping station in the rotary die method and
Figure 3 the symbolic representation of a double screw-type ex¬truder with the temperature conditions prevailing therein.
Figure 4 shows Young"s modulus of elasticity E [MPa] of a ho¬mogenised mass containing a starch according to the in¬vention, in dependence on the temperature (conditioned 50% relative humidity).
The measurement of the elongation at rupture and Young"s modulus of elasticity E is performed according to DIN Standard 53455 re¬spectively DIN EN ISO 527-1 to ISO 527-3. The measurement of the elongation at rupture is performed according to this DIN stan¬dard at the corresponding encapsulation temperature.
The measurement of the limiting viscosity number [nJ is per¬formed analogously to the DIN Standard: DIN 51562-1 to 51562-4. However the softener content of the samples and its influence on the run-through times in the Ubbelohde vicosity meter now had to be taken into account. For this firstly the influence of the softener content on the run-through time to was determined, by way of the obtained calibration lines then the run-through times tosoftener could be Calculated with any softener content according to
tosoftener = t o " ( 1 ■ 0 0 0 02 + 0 . 0 02 3 8 - Cgoftener)
wherein Caoftener is the concentration of softener present, in mg/ml. The limiting viscosity number determined for Che broken down starches together with the mechanical properties of the as¬sociated samples are set up in Table 1.

The manufacture of the samples which in Figure 1 demonstrates the connection between the elongation at rupture and the limit¬ing viscosity number, is effected in the following manner
starch: 56.2 to 56.9% by weight
glycerine: 41.8% by weight with respect to the content of the
water-free starch water: 1,3 - 2.0% by weight with respect to the total
weight of the mixture.
The mixtures were homogenised in a Brabender kneader at 160 rpm with a kneading time of in each case 15 min and at variable kneading temperatures of llCC, 160""C, 200=0, 220°C and 235°C.
Figure 1 shows the dependency of the elongation at rupture of the mass containing starch on the limiting viscosity number of the starch. From Figure 1 and the associated Table 1 it is evi¬dent that with an increasing temperature in the Brabender kneader the limiting viscosity number of the starch reduces, i.e. with an otherwise unchanged composition and unchanged proc¬ess parameters (only variable is the temperature) the degree of breakdown of the starch increases. 97% elongation at rupture is reached at a limiting viscosity number of 82.8 ml/g. Thereafter the elongation at rupture with an increasing value of the limit¬ing viscosity number runs asymptotically to a limit value of ap-prox. 105%.
The initial value of the limiting viscosity number, i.e. the value from which a noticeable rise of the elongation at rupture is observed is independent on the softener constituent part and singly dependent on the molecular weight average of the starch molecules or the corresponding limiting viscosity number.

with a lower content of softener the shape of the graph flattens i.e. the graph is shifted to lower values of the elongation of rupture.
Even when the limiting viscosity number of the whole mass is measured, the value of the number is essentially dependent on the polymerisation degree of the starch. The value of the limit¬ing viscosity number is essentially independent of the remaining components of the mass (or their low influence may mathemati¬cally be taken into account).
The maximal strength a^ was evaluated analogously to DIN standard 53455 and DIN EN ISO 527-1 to ISO 527-3. Also a^, exhibits a de¬pendency on the limiting viscosity number, i.e. the degree of breakdown of the starch. The lower the limiting viscosity number with otherwise unchanged conditions is, the lower is c^.
The filling and shaping station indicated as a whole at 1 in Figure 2 comprises for the encapsulation a shaping drum pair 6, 6", wherein in the surface of the shaping drums there are ar¬ranged the recesses necessary for shaping the capsules. In the entry let-in of the shaping drum pair there is arranged a fill¬ing wedge 5 through which by way of a delivery pump 5 the fill¬ing material may be introduced. With the present embodiment ex¬ample the capsule casing consists of two layers with different material properties which are formed by the two starch films 7a, 7a" on the one hand and 7b, 7b" on the other hand. These two starch films are prepared in the worm-type extruders 2a, 2a" and 2b, 2b" and via diverting drums 3, directly and with the same conveying speed, are led to the entry let-in of the shaping drum pair 6, 6". The worm-type extruders are with this arranged next

to the filling and shaping station and where appropriate ar¬ranged on the same machine frame.
The starch films are between the shaping drum pair shaped and welded into a one-part soft capsule, wherein they enclose the filling material. The individual capsules 9 are collected and in any case led to a drying process whilst the remaining film skeleton 8 possibly by recycling is again processed to new cap¬sules .
The direct arrangement of the extruder next to the shaping and filling station and the „inline" supply of the extruding film into the shaping and filling station (without intermediate stor¬age) is of course possible at any time, thus also with the manu¬facture of single-layered capsule casings (usual rotary die method).
Figure 3 shows in a heavily simplified manner a double worm-type extruder 10 which in the present case is composed of twelve in¬dividual housing blocks 1 -12. The housing blocks are continu¬ously numbered from left to right. Each housing block may be electrically heated with a separate control circuit and/or be cooled with valve-controlled influxes with cold water. Further¬more individual blocks may be provided with connection pieces as will yet be explained hereinafter. In the present case it is the case of equally rotating, tightly meshing double worm-type ex¬truders, wherein the diameter of a worm is 44 mm. The length of the whole worm shaft is 2,112 mm, which corresponds to a ratio of length to diameter of 48. At the end of the extruder the ma¬terial is delivered via a nozzle 14. This nozzle may for example comprise twelve hole bores of 2 mm diameter. At the same time it would be conceivable for the manufacture of the granulate to hot-sprue the individual material lines and then lead them to a

fluid bed dryer. At the nozzle 14 however also directly a fin¬ished material film may be removed.
On the worms 12 at suitable locations there are arranged knead¬ing disks 13 of differing configurations in order to achieve as homogeneous as possible kneading of the material mixture. The block 1 is cooled with water and provided with a powder feed 15. The block 2 is closed whilst on block 3 there is arranged an in¬jection nozzle 16 for a fluid metering into the kneading space. In the transition region of the blocks 2 and 3 there are ar¬ranged fine neutral kneading disks 13. The blocks 4 to 6 are again closed, wherein on block 5 there are provided broad, neu¬tral and back-conveying kneading disks. Block 7 has at its dis¬posal a connection conduit 17 which is connected to a vacuum source. On block 8 again there is arranged a powder feed 18 and the worm is provided with a fine, neutral and/or conveying kneading disk. Block 9 likewise has at its disposal an injection nozzle 19 whilst block 10 is closed. The worm in block 10 in contrast has at its disposal broad, neutral and back-conveying kneading disks. Block 11 has a further connection conduit 20 which may be connected to a vacuum source or to the atmosphere. Block 12 is closed, the worm here however has medium, conveying kneading disks.
Below the schematic conveying worm there is drawn up a tempera¬ture curve. The adjustable temperature accuracy is +/- 3°C. With the specified temperatures it is the case of the block tempera¬ture which does not compellingly need to be identical to the temperature in the molten mass. The temperature in the molten mass is evidently still influenced by other parameters, in par¬ticular by the rotational speed of the worm. With the extrusion it is therefore necessary to take account of these conditions

and to match the adjustable variables to one another such that optimal material properties are achieved.
With the embodiment example described by way of this Figure a rotational speed of 340 revolutions per minute (rpm) is made. The total throughput is approx. 34.3 kg/h and the energy uptake approx. 0.175 kWh/kg. To the block 1 held at 20°C there is me¬tered 20 kg/hour (approx. 60%) of starch powder. The powder is entered with shifting edges and then supplied to the blocks 2 and 3 heated to 100°C. With block 3 there is effected a metering of 11 kg/h {approx. 3 0%) glycerine with a working pressure of at least 10 bar via a gravimetric piston pump. In the closed blocks 4 to 6 the temperature is increased to 140°G. With block 7 there is applied a vaccum of 800 mbar, wherein approx. 6% water exits. The temperature is now again taken back to 110°C. With block 8 there is effected a supply of 1.4 kg/h {approx 10%) of calcium carbonate. Where appropriate at block 9 1.9 kg/h {approx. 5 to 8%) of glycerine may be metered. The working pressure is like¬wise at least 10 bar. If this connection is not required it is closed with a blind plug. At block 11 again there is applied a vacuum, wherein approx. 2 to 4% water exits. Where appropriate an atmospheric aeration is also sufficient.
The temperature of the molten mass may at no location of the ex¬truder exceed 160*"C since otherwise a thermal breakdown of the starch sets in. Furthermore it is the case that the thermal change of the starch is smaller, the shorter the molten mass is subjected to a higher temperature. Therefore an optimal relation between temperture control and material throughput must be cre¬ated.
In Figure 4 there is shown the temperature dependence of Young"s modulus of elasticity E. The composition of the test samples

corresponds to Example 2 {unbroken line). In comparison thereto the theoretical temperature behaviour of a thermoplast of a similar glass transition temperature is represented. Whilst the modulus of elasticity of the „normal" thermoplast (dashed line) falls rapidly linearly to zero, with the test samples the modulus of elasticity in a region of 40°C to approx. 70°C is al¬most independent of the temperature. This behaviour is amongst other things also responsible for the advantageous properties of the present invention
The present invention is further explained by way of the subse¬quent examp1e s:
Example 1
Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition:
starch: 7.7 kg/h
lecithin: 0.147 kg/h
glycerine monostearate: 0.147 kg/h
glycerine (99.5 purity): 4.47 kg/h
calcium carbonate, precipitated: 1.0 kg/h
wherein with a worm rotational speed of 180 rpm one extruded un¬der the following conditions (see Figure 3):
block 1: 25°C
block 2 and 3 100°C
block 4 to 6 140°C
block 7 to 9: llCC
block 10 to 12: 110°C

nozzle: 110°C
With respect to the water-free starch this corresponds to a glycerine content of 38.77%, With respect to the water-free end product there resulted the following constituent parts:
lecithin: 1.11%
glycerine-raonostearate 1.11%
starch (water-free): 55.15%
CaCOa: 7.76%
glycerine: 34.87%
Specific energy uptake on extrusion: 0.275 kWh/kg
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [ri] of the starch in the starch containing mass is 107,2 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 102% +/-10%.
Example 2
Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition:
starch: 7.7 kg/h
lecithin: 0.147 kg/h

glycerine monostearate: 0.147 kg/h
glycerine (99.5 purity): 4.67 kg/h
Wherein with a worm rotational speed of 260 rpm one extruded un¬der the same conditions as in Example 1.
In block 4 alternatively a vacuum may be applied in order to re¬move excess water (from the starch powder) (e.g. 800 mbar).
With respect to the water-free starch this corresponds to a glycerine content of 39.81%. With respect to the water-free end product there resulted the following constituent parts:
lecithin: 1.18%
glycerine monostearate 1.18%
starch (water-free): 58.81%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [r\] of the starch in the starch containing mass is 115,6 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 107% +/-10%.
Exan^le 3
Via a two-shaft extruder (type ZSK 30, Werner & Pfleiderer) the following components were continuously metered and processed to a thermoplastically processable condition:

All details in % by weight
starch: 57.88%
lecithin: 1.06%
glycerine monostearate: 1.06%
glycerine (98% purity): 3.64%
sorbitol syrup (containing 30% water) 36.36%
wherein one produces under the following parameters
worm rotational speed of the two shaft extruder = 150 r.p.m. Into the blocks 7 and 10 via a vacuum pump there was applied a pressure of 400 mbar in order to remove excess water {which amongst other things is introduced into the product via the moisture content of the starch and of the sorbitol syrup).

Block temperatures block 1: block 2 and 3: block 4 & 5 block 6 & 7 block 8 & 9 block 10-12 nozzle:

20°C
iio°c:
140°C 120""C 110°C lOO^C 95°C

The specific energy uptake on extrusion was 0.195 kWh/kg
With respect to the water-free end product there results the following composition (all details in percentage by weight):

starch (water-free): lecithin:

61.25% 1.31%

glycerine-monostearate: 1.32%
glycerine: 4.44%
sorbitol: 31.69%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [ri] of the starch in the starch
containing mass is 92,5 ml/g +/- 5%. The extruded film has an
elongation at repture at capsule forming conditions of 107% +/-
10%.
Example 4
Extrusion conditions as in Example 3 and the following dosages:
Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition:
All details in % by weight

starch:
glycerine monostearate:
glycerine (98% purity):
sorbitol syrup {containing 30% water):

58 .92%
1 .08%
3 .64%
36. 36%

The specific energy uptake on extrusion was 0.265 kWh/)cg
With respect to the water-free end product there results the following composition (all details in percentage by weight):

starch (water-free): 62.46%
glycerine-monostearate: 1,35%
glycerine: 4.44%
sorbitol: 31.75%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [T\] of the starch in the starch containing mass is 126,3 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 156% +/-10%.
Example 5
Extrusion conditions as in Example 3 and the following dosages:
Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously and processed to a thermoplastically processable condition:
All details in % by weight.
starch: 62.95%
glycerine monostearate: 1.15%
glycerine (98% purity): 8.28%
sorbitol (30% water content) 27.61%
The specific energy uptake on extrusion was 0.295 kWh/kg

With respect to the water-free end product there results the following composition (all details in percentage by weight):
starch (water-free): 65.17%
glycerine-monostearate: 1.40%
glycerine: 9.89%
sorbitol: 23.54%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [T\] of the starch in the starch
containing mass is 79,3 ml/g +/- 5%. The extruded film has an
elongation at repture at capsule forming conditions of 203% +/■
10%.
Example 6
Extrusion conditions as in Example 3 and the following dosages:
Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition:
All details in % by weight
starch: 55.80%
glycerine monostearate: 1.02%
glycerine (98% purity): 3.93%
sorbitol sirup (containing 30% water): 19.63%
maltitol syrup (containing 25% water): 19.63%

The specific energy uptake on extrusion was 0.225 kWh/kg
With respect to the water-free end product there results the following composition (all details in percentage by weight):
starch (water-free): 58.73%
glycerine-monostearate 1.26%
glycerine: 4.76%
sorbitol: 17.01%
raaltitol: 18.23%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [r\] of the starch in the starch containing mass is 74,8 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 184% +/-10%.
Example 7
Extrusion conditions as in Example 3 and the following dosages:
Via a two-shaft extruder (type ZSK 25, Krupp, Werner & Pflei-derer) the following components were continuously metered and processed to a thermoplastically processable condition:
All details in % by weight
starch: 59.88%
glycerine monostearate: 1.10%

glycerine (98% purity): 3.55%
sorbitol sirup (with a high constituent part of hydrated oligosaccharides): 17.74% sorbitol (containing 30% water) 17.74%
The specific energy uptake on extrusion was 0.185 kWh/kg
With respect to the water-free end product there results the following composition (all details in percentage by weight):
starch (water-free): 63.36%
glycerine-monostearate 1.37%
glycerine: 4.33%
sorbitol: 15.46%
sorbitol with a high constituent part
of hydrated oligosaccharides: 15.46%
The extruded film is suitable for the production of shape arti¬cles irrespective of the specific form. Particularly suitable are the films for the production of soft capsules with a one-part capsule casing in the rotary die process.
The limiting viscosity number [r]] of the starch in the starch containing mass is 88,1 ml/g +/- 5%. The extruded film has an elongation at repture at capsule forming conditions of 240% +/-10%.

Tab.l

The mechanical properties of the starch film with 41.8% glycerine in dependence on the limiting viscos¬ity number [TIJ

°C H2O
% [tl] ml/g d mm CTTH
MP a %
110 1.77 160.5 0.72 7.0 +/- 0.3 107 +•/- 6
14 0 1.80 139.9 0.65 6.8 +/- 0.4 106 +/- 18
160 1.55 127.9 0.64 6.3 +/- 0.4 99 +/- 5
180 1.54 115.6 0.64 6.9 +/- 0.2 107 +/- 9
220 1.66 82.8 0.73 4.8 +/- 0.4 97 +/- 23
200 1.55 59.2 0.61 4.9 +/- 0.5 69 +/- 23
235 1.30 51.5 0.87 9.0 +/- 0.7 22 +/- 24

Documents:

in-pct-2002-0726-che abstract duplicate.pdf

in-pct-2002-0726-che abstract-duplicate.pdf

in-pct-2002-0726-che claims duplicate.pdf

in-pct-2002-0726-che claims-duplicate.pdf

in-pct-2002-0726-che correspondence-others.pdf

in-pct-2002-0726-che correspondence-po.pdf

in-pct-2002-0726-che description(complete)-duplicate.pdf

in-pct-2002-0726-che description(complete).pdf

in-pct-2002-0726-che drawings.pdf

in-pct-2002-0726-che form-1.pdf

in-pct-2002-0726-che form-19.pdf

in-pct-2002-0726-che form-26.pdf

in-pct-2002-0726-che form-3.pdf

in-pct-2002-0726-che form-4.pdf

in-pct-2002-0726-che form-5.pdf

in-pct-2002-0726-che petition.pdf

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Patent Number

202444

Indian Patent Application Number

IN/PCT/2002/726/CHE

PG Journal Number

05/2007

Publication Date

02-Feb-2007

Grant Date

11-Oct-2006

Date of Filing

17-May-2002

Name of Patentee

M/S. SWISS CAPS RECHTE UND LIZENZEN AG

Applicant Address

Hausenstrasse 49 CH-9533 Kirchberg

Inventors:

#	Inventor's Name	Inventor's Address
1	Dr. Ivan TOMKA,	Schaffhauserstrasse 219 CH-8057 Zurich
2	Dieter, Wolfgang ENGEL,	Eschenstrasse 38, 9524 Zuzwil
3	Dr. Erich BROCKER,	Lerchenfeldstrasse 190, 9533 Kirchberg
4	Rico MENARD,	Schanzweg 4d, 9533 krichberg

PCT International Classification Number

A61K 9/48

PCT International Application Number

PCT/CH2000/000616

PCT International Filing date

2000-11-16

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	99811071.2	1999-11-19	EUROPEAN UNION