Indian Patents. 206580:POWDER COMPACTION AND ENROBING

Title of Invention	POWDER COMPACTION AND ENROBING
Abstract	Powder. e.g. of a medicament, is compacted and enrobed to product compacted powder sings by preferably me charucally compating a powder and forming a film of material. prefrably hydroxy pxopyl methyl cellalose, by Vacum or pressure differintial, about the surface of the powder thus compacted.

Full Text	Powder Compaction and Enrobing Field of the Invention this invention concerns the compacting of powder e.g. a powder containing a medicament, vitamin, dietary supplement etc, and such compacted powder being enrobed by a biodegradable and/or water soluble film, for example a non gelatin film, such as bydroxypropyl methyl cellulose (HPMC) , to produce encapsulated bodies of compacted powder, suitable for dosage foras, e.g. for human ingestion. The invention is applicable to all related dosage forms, including tablets, but for simplicity all auch forma will be generally referred herein as capsules. Background to the Invention Tablets are a common type of dosage form and various means for improving their properties have been tried. Current methods for coating tablets, such as pharnaceutical tablets include the using of acelacoaters ox pan coaters. which spray low molecular weight HPMC grades onto tablets so iaparting a surface layer, which as uniform and smooth, but opaque and of low gloss. It is possible for the tablets to have embossed lettering on them. This method of coating tablets is however very time consuming and requires a high level of expertise to produce satisfactory results. Production complications such SUBSTITUTE SHEET (RULE 26) 2 as tablet twinning are common, where two tablets becone attached to one another during the spray coating operation. In addition to thQso problems it is necessary to compact the tablets under relatively high pressures so that they do not disintegrate during the coating process. This high level of compaction can have an adverse effect on the disintegration and dissolution rates of active ingredients contained within the capsule, for example, leading to a delay in the release of a drug to a patient, whilst the tablet slowly dissolves in the stomach of the patient. An alternative Co spray or pan coating is to use two-piece hard capsules. These are produced by a dipping process, typically a HPMC solution is used, producing half shells which interlock and thus produce an enclosed capsule. These capsules are typically opaque but glossy, and cannot have any form of embossment, as this would interfere with the overlap interlocking process. The nature of the capsule dictates that there will always be an airspace above the powder fill level. Additionally, it ia not possible to compact the powder .into these tablets, and this so limits the quantity of powder which can be encapsulated. It follows that this lack of compaction can effectively reduce the amount of e.g. medicament which can be encapsulated. The existence of the air space in the capsule and lack of compaction of the powder contained within the capsule leads to a capsule that 13 inevitably larger than necessary. SUBSTITUTE SHEET (RULE 26) It has also been found that, after manufacture and/or' sale of two-piece hard capsule3, the capsules can be easily and illegally interfered with, as it is possible to separate the two halves of the capsule and tamper with its contents and replace the two halves back together without there being any obvious change in the capsule's external appearance such to suggest to the user that there was anything wrong with the capsule. This means that it can be difficult to detect capsules which have had their contents tampered with. KPMC and certain other non-gelatin materials are suitable for ingestion by humans, so delivery capsules with gelatin walls find potential use as ingestible capsules, e.g. for the delivery of accurately metered doses of pharmaceutical preparations and dietary supplements, AS a possible replacement for gelatin based capsules. Conventional tablets have already been enrobed. See for example WO 02/098394. Summary of the Invention One aspect of the invention concerns a novel method for compacting and enrobing a powder to produce capsules with enhanced properties. A non gelatin film layer is thermo.foxmed into a suitable tablet shaped pocket under the influence of heac and/or vacuum, and/or pressure. A pre-determined mass of powder is dosed into the film formed pocket, and compressed into a SUBSTITUTE SHEET (RULE 26) 4 tablet shape e.g. with the aid of a piston or pistons. A partially enrobed 'soft' tablet results from this process, which is then fully enrobed by a second sequence of events which involves the raising of the tablet above a platten which allows the remainder of the compressed tablet to be enrobed by a second film. Suitable tablet shaped pockets can be created by using e.g. a pair of pistons slideable within a cylinder, such pistons also having the advantage of being able to form pinch points between the platen and the top of cylinders which are useful for cutting away unwanted excess film from the (partially) enrobed tablets. One of the aims of "the present invention is to produce taaper evident capsules. Another aim of the present invention is to produce powder filled capsules whereby the powder is enrobed with a material which may or may not form a skin tight wrap'. Another aim of the present invention is to produce a capsule with a high gloss surface which is able to adopt an underlying embossment, e.g. to identify a pharmaceutical tablet. Another aim of the present invention is to produce capsules which have a flange which is almost non-discernable. SUBSTITUTE SHEET (RULE 26} 5 Another aim of the present invention is to enable the' production of dosage forms in a wide variety of shapes and sizes, which , because of the nature of the processes involved and the properties of the product produced, includes shapes and sizes of dosage forms which have not been previously possible to make or practical to use. Another aim of the present invention is to produce capsules with favourable properties and which contain powd.es or other flowable solid material which is at a favourable state of compaction and/or composition, and/or the encapsulating medium of the capsule being fast dissolving or dissolvable(with control) pharmaceutical grade films plasticised with pharmaceutical grade materials. Another aim of the present invention is to produce capsules, which by their nature, are easy to swallow, and more easily can be conveyed to the site where it is desirable where tne active ingredients are most advantageously released. Another aspect the present invention is a method of powder compaction to produce powder compacted slugs, which , for example can be enrobed to produce capsules which possess enhanced disintegration and dissolution properties over and above traditional tablets. SUBSTITUTE SHEET (RULE 26) Another aspect of the present invention is a method of producing a capsule, which, at the very least can perform the same function as * conventional coated tablet, but in which the conventional tablet pressing and coating stages are replaced by a single powder enrobing process. Another aspect of the present invention is a method of producing a capsule by enrobing powder, in which, because of the nature of capsule produced, certain ancillary ingredients necessary in conventional tablet production, can be omitted. For example, ingredients in a tablet which are added to give the tablet its structural integrity can be omitted, because the active ingredients are in powder form, relatively loosely compacted are encapsulated within a film, such film which now securely packages the powder/ ingredients, thus giving integrity and forming a discrete effective dosage form. Because of the aforementioned, components contained within a tablet which are designed to disperse and break up the tablet when it has reached the site of delivery, can be omitted, as the active ingredients in the capsule according to the present invention arts in a non-compacted or at least less compacted form as compared to a conventional tablet, and this lesser compaction leads to the easy release and dispersal of active ingredients once the capsule film has dissolved, e.g-at the. intended site of delivery. SUBSTITUTE SHEET (RULE 26) 7 Another aspect of the invention provides a method of enrobing compacted powder, comprising vacuum forming a film into a pocket, compacting a powder in said pocket, resulting in a partially enrobed powder slug in a pocket. Vacuum forming a second film over this powder slug to completely enrobe the powder slug, forms a discrete compacted powder filled capsule, suitable for use as a dosage form. In yet another aspect of the present invention provides a method of enrobing compacted powder using film or films, to form a compacted powder filled capsule, wherein the film or films forming the wall of the compacted powder filled capsule used overlap each other. In a further aspect of the pxesent invention provides a method of forming and/or enrobing a compacted slug wherein the level of compaction of the compacted powder is less than that necessary to reach the industry standard for the discrete slug of compacted powder to be described as a tablet. In practising the method of the invention, the films are caused to deform to conform with the external surface of the pocket and the compacted powder slug, the films effectively forming a secure capsule, by being wrapped around the powder slug, vacuum chamber or vacuum bed apparatus, in which the films and powder are located in a suitably shaped support and SUBSTITUTE SHEET (RULE 26) 8 exposed to conditions of vacuum (or substantially reduced pressure) can be modified and used for this purpose. 'Such apparatus may be based on commercially available vacuum chamber or vacuum bed apparatus, suitably modified- Vacuum forming techniques result in the compacted powder being completely enclosed and encapsulated within a film, leading to a capsule containing compacted powder, such capsule having enhanced and controllable properties over dosage forms currently available, such as conventional tablets. The powders to be compacted are typically.subjected to pressures between, but not limited to, 5-15 mega pascals. Examples of powders compacted and enrobed include paracetamol, ibuprofen, sorbitol and multivitamin. Other powder fill3 which are contemplated are antacid, anti-inflammatory, anti-histamine antibiotic and anti-cholesterol drugs. The film should be a material which is suitable for human consumption end that has sufficient flexibility and plasticity to be vacuum formable. Some film materials have suitable properties in their natural condition, but commonly it will be necessary to pre-treat the film material so that it is vacuum formable. For example, it may be necessary to expose the film material to a solvent therefor; for instance certain grades of polyvinyl alcohol (PVA) will vacuum, form after application of a small amount of water to the surface thereof or when exposed to conditions of high humidity. A SUBSTITUTE SHEET (RULE 26) 9 further generally preferred possibility, is to use a film of thermoplastic material (i.e. material capable of deforming plastically on Seating) with the film to be in heat-softened condition prior to being thennoformed by exposure to vacuum-Suitable thermoplastic materials include modified cellulose materials, particularly hydroxypropyl methyl cellulose (HPMCJ and hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA) , polyethylene oxide (PEO) , pectin, alginate, starches, and modified starches, and also protein films such as soya and whey protein films. The currently preferred film material ia HPMC. Suitable film materials are currently available. When using thermoplastic film, the film as typically heated prior to application to pocket or compacted powder slug, so that the film is in a heat softened deformable condition. This can be achieved by exposing the film to a source of heat e.g. an infrared heater, infrared lamps, a heated plate a hot air source etc. In the process described, a range of temperatures may be used, but by way of example only, whore films of different thickness may bo utilized for the first and second films in the process, a first film forming temperature of around 150 degrees centigrade may be used and for the second film forming stage, a range of approximately 70-80 degrees centigrade may be used. SUBSTITUTE SHEET (RULE 26) 10 During the enrobing process, films may be caused to overlap, preferably a minimum of 1.5mm-2mm. Compacted powder slugs may preferably have a sidewall height of about 3mm and films may be caused to overlap substantially completely over the sidewall area. The film material may include optional colourings, e.g. in the form of food dyes auch as FD and C yellow number S, and/or optional flavourings, e.g. sweeteners, and/or optional textures etc in known manner. The film material typically includes plasticiscr to give desired properties of flexibility to the film in known manner. Materials used as plastlcisers include alpha hydroxy acids such as lactic acid and salts thereof, roaleic acid, benzyl alcohol, certain iactones, diacetin, triacetin, propylene glycol, glycerin or mixtures thereof. A typical thermoplastic film formulation is HPMC 77 by weight, plasticiser 231 by weight. The film suitably his a thickness in the range 20-200 microns, conveniently 50 to 100 microns, e.g. at about 80 microns, with appropriate film thickness depending on factors including the size and form of the tablet. Films of different thickness may be used, e.g. a film of greater thickness may be used in the first stage of the enrobing process, say 125 SUBSTITUTE SHEET (RULE 26) 11 microns thickness and a film of lesser thickness may be used in the second stage of the enrobing process, say 80 microns thickness. Because of the nature of the film forming process according to the present invention, under certain circumstances, e.g. where the powder to be compacted contains particles which, under compaction, have the ability to pierce film, it may be advantageous to have the thickness of the film formed in the pocket to be greater than, that of the film which is to cover the remainder of the compacted powder slug {in the second ant final phase of enrobement of the compacted powder). Such differential thickness may give rise to certain advantageous structural features of the resultant capsule; the capsule my be generally more robust and 30 may be more safely stored and handled I generally thicker film on the capsule ), but such cap9ule also possessing a smaller araa (window} of weaker, thinner film which can give rise to quicker release characteristics by the thinner film will dissolving more quickly when exposed to any given solvent. An advantageous differencial film thickness to form a capsule with wall of different thickness, could be e.g. 70/90 micron film coordination to produce cap3ules which are robust but which release their contents caiickly, through a window of thinner film. Therefore films of different thickness may be used in the enrobing process, and to give a further examples, a film of SUBSTITUTE SHEET (RULE 26) 12 greater thickness may be used in the first stage of the enrobing process, a maximun of 200 microns and a minimum of 70 microns but say preferably 125 microns thickness and a film of lesser thickness may be used in the second stage of the enrobing process, a maximum of 125 nicrons and a mlninun of 50 microns, but say preferably 80 microns thickness. Wben making multiples of enrobed compacted powder slugs , the spciog of the compacted powder slugs can be important. If the compacted powder slugs are position ed too closely together, the film is not able to fully thermoform between them. For example, a spacing between the adjacent compacted powder slugs of about 4mm has been found to give good results, the film being able to fully adopt the vertical sidewall of the compacted powder slug to a distance of about 2mm before it begins to curve away from the side of the compacted powder slug. According to one aspect of the invention , the method involves forming two separate overlapping half coatings of film, effectively on the compacted powder slug. The method preferably involves, first forming a film in a pocket, then compacting a powder slug into the film lined pocket, thereby effectively coating/encapsulating a substantial portion of a SUBSTITUTE SHEET (RULE 26) 13 powder slug within a film formed into a partial capsule, removing tbe regaining film material not coating the' compacted powder slug e.g. by cutting, then coating the remaining half of the compacted powder slug, with overlapping portions of the two coatings sealed together to provide a 3ealed complete enclosure for the slug, and again removing remaining surplus film material not coated on the slug. It may be necessary to apply adhesive material between the overlapping film coatings e.g. to the surface of the film layers, to ensure the formation of an effective seal therebetween and to make the resultant capsule tamper-evident. The adhesive material conveniently has the same composition as the film, but with a greater proportion of plasticiser, e.g. 93% to 98% by weight plasticiser, so as to provide a less viscous material. The adhesive material may be applied, e.g. by use of a roller, spraying etc. A typical adhesive fonr.ulation, with & representing % by weight, is HPMC 4%, lactic acid 77%, water 19%. The compacted powder slug and capsule conveniently include a generally cylindrical side wall portion, with two half coatings overlapping on this side wall. Tablets of circular symmetrical form with a circular cylindrical side wall are very common, but other forms e.g. generally oblong and oval, again including a generally cylindrical side wall, are also Known. SUBSTITUTE SHEET (RULE 26) 14 It nay be also advantageous or desirable to apply adhesive material e.g. as described above, to the surface of compacted powder slug prior to the final stage of coating, to promote adhesion of the second portion of the film thereto. Again, this may be achieved by e.g. use of a roller, spraying etc. A plurality of tablets in an array may be conveniently coated simultaneously, using a suitably large sheet of film material. BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS This invention is now further described in detail, by way of example only, with reference to the drawings. Steps a-k show the basic compaction and enrobing apparatus and process. The drawings show the various stages of a powder compaction/enrobing process. Figure 1 shows the mechanism of the basic steps of powder compaction and entoboraent: via steps a-1: a. A first film (1) is laid upon a platten (2). Lower piston (3), slideable in cylinder (4) incorporates vacuum port (5). b. Film (1) completely drawn down into cylinder (4) by a vacuum created by vacuum port (5) and said film (l) also SUBSTITUTE SHEET (RULE 26) 15 resting on the crown of lower piston (3), to form a pocket shape. c. A quantity of powder (6) is introduced over the pocket of film and upper piston (9) moves downward towards the lower piston (3) compressing a quantity of powder {€) d. A compacted powder slug (7) resulting from the completion of step c. e. Cutting of film by the introduction of cutting tool (10) to torm an isolated semi enrobed slug of compacted powder. f. Lower piston (3) begins to move upwards, thereby also urging compacted powder slug (7) upwards. g. Lower piston (3) comes to rest, positioning compacted powder slug (7) proud of platen (2) h. Introduction of a second film (8) over platen (2)and also loosely stretching over compacted powder slug (7) i. Second vacuum is applied drawing second film (8) around and closely in association with the upper portion of compacted powder slug (7), second film {8) thereby wrapping itself around the upper part of the compacted powder slug (7). j. Cutting tool (12) descending and trimming off excess unwrapped film from powder slug (7). k. Fully enrobed powder slug, has been ejected from cylinder(4)by the further upward movement of lower piston (3) and has the loose ends of the films ironed and sealed by irons (13) . SUBSTITUTE SHEET (RULE 26) 1. Shows a fully enrobed tablet with ironed seams. Figure 2 depicts a variation of the basic process described by figure 1. Steps al and bl show a second pre-forned film pocket, formed by a second vacuum forming pocket (14) being lowered onto the platten immediately above a partially enrobed powder slug as shown in step f of figure 1. Once the opposing film pocket is in position lower piston (3) moves upwards thus pushing compacted partially enrobed powder slug also upwards and into the cavity of the second pre-formed film pocket, thus capping the partially enrobed powder slug to form a fully enrobed capsule, enrobed by two pockets of film. The capsule is then released , trimmed and ironed as mentioned previously. Figure 3 depicts a further variation of the basic process described by figure 1. Step a2 shows a powder slug as in step f of figure l, and Like figure 2 a second pre-formed film pocket is introduced, but this time it is a shallow pocket, forced by a second shallow vacuum forming pocket (15), such to only coat the top of the powder slug and to form a. seal at the circumference of ths very edge of the cylindrical SUBSTITUTE SHEET (RULE 26) 17 portion of the powder slug. Steps a2-d2 show this revised process. This process gives rise to a capsule with a different type of seal which gives rise to different properties in the capsule. Figure 4 depicts another variation of the process described by figure 1. However the basic process is essentially duplicated to form a capsule which contains two distinct half doses of powder. The basic process as described in figure ) is carried out up to step f, in duplicate, which is basically steps a3-c3 in figure 4. The main differences at this point in figure 4, are that the two opposing pockets filled vith compacted powder (16,17) ate half size in depth, and the top of the powder slugs are essentially flat, rather than rounded. Step c3 may include the laying down of an intermediate film on the surface of the half slug. Steps d3-f3 show the bringing together of 2 half slugs to form a single capsule, comprised of 2 parts Step q3 shows a compartmentalized capsule. The advantages ace at least 2 separate doses of active ingredients can be incorporated into 1 capsule, under pechaps different compaction pressures etc. This gives rise to further flexibility and options as to the performance of the new dosage forms. 18 The process described, and in conjunction with the quantity of powder used, with the careful positioning of the co-acting pistons during the compaction process/ can facilitate the formation of powder slugs having various levels of compaction. As previously described, these varying levels of compaction are allowed in the powder slugs because the slugs are enrobed within a film, and it is this film enrobement which provides the slug with the necessary integrity it needs so that it can function as a convenient and stable dosage form. The process and apparatus can be modified such to produce capsules with varying properties, which have advantages over tablets and conventional capsules already known in the art. For exanple, a capsule according to the present invention containing a powder with a low compaction, could produce extremely favourable quick release characteristics, suitable, e.g. for a fast acting analgesic; the film can be both designed to be smooth/flexible, to allow the capsule to quickly and relatively painlessly travel to the intended site of drug delivery through the digestive tract, and also be designed to dissolve at or neax the intended site of drug delivery. The lower compaction of the powder in the capsule can also aid smooth travel of the capsule in the digestive tract, as the contents of the capsule can be designed to be compressible and mobile, thus 19 allowing the capsule to be bent and/or compressed as it travels through the body so that it can conform to th'e 3hape of a more restricted part of a. passage, squeeze through it and so continue its journey through the digestive tract with leas hindrance. Such dosage forms may find themselves especially useful where a patient finds difficulty in swallowing, has a painful or restricted digestive tract, or there is some ether reason why a dosage form is required to be more mobile and less aggressive to the internals of the body. The following methods are given by way of example and it is not intended to limit the invention in any way: Example 1 Consumable items: Film 1 - 125micron thickness, hpmc plasticised with lactic acid 15%, and triacetin 5%, processing aids starch 1% and aorbitol monostearate 0.25%. Film 2 as film 1 but 80 micron thickness. Glue applied to overlap area of first film - benzyl alcohol 45$, triacetin 50%,hpmc El5 Premium (Dow Chemical Corp.) 5% SUBSTITUTE SHEET (RULE 26) 20 Process description Film 1 is thermofonned into single or multiple tablet/caplet shaped pockets m a platen, each pocket containing a lower piston that can be raised or lowered as necessary to suit standard sized tablets and caplets. The tablet shaped pocket also has a raised edge profile around the top perimeter of the pocket. Thi3 edge profile is raised Irani above the platen surface and has a land width of 0.35mm. The vertical sidewall of these pockets is typically 3niin deep. The thermoforming operation involves the film acting as a membrane dividing the two halves of a vacuum chamber, which are separately controlled. . The chamber above the film contains a flat heated platen at a temperature of approximately 150°C. Vacuum is drawn above the film causing it to be held against the heated plate for a period of 1 to 5 seconds preferably 3 seconds. The vacuum xn the upper chamber is maintained whilst vacuum is also applied to the lower chamber. At this stage the film remains against the heated platen. Once the vacuum level in the lower chajnber reaches at least -0.65 bar the vacuum in the upper chamber is released to atmosphere or replaced by positive pressure, this forces the film downwards away from the heated platen and onto the tablet pocket shaped tooling below. In this way the film adopts the shape of the tablet pockets in the lower tooling. SUBSTITUTE SHEET (RULE 26) *1 Powder dosing and film 1 cutting A dosing assembly is then placed over the film formed pocket. This consists of a location mask which sits on location dowels in the platen, and a dosing sleeve that rests directly above the film formed pocket, and aits on the raised edge profile. The dosing sleeve exactly matches the dimensions of the film formed pocket. A dose of powder is deposited into the dosing sleeve and falls into the film pocket. Compaction is achieved via a compaction piston that advances through the dosing sleeve and sweeps any residual powder down into the film pocket below and compacts it to a fixed stop, such that it does not cut the film, but instead comes to rest, directly adjacent to the film. The level of compaction is controlled by the mass of powder being deposited into the dosing sleeve. The piston below the compacted powder tablet is then lowered and either the compaction piston is advanced by a similar amount causing a punch cut through the film as it interferes with the inside or the raised edge profile. Alternatively the compaction piston is replaced by a cut piston which similarly advances and causes a punch cut with the raised edge profile. The fit tolerance between the cut piston and the internal dimensions of the raised edgs profile are such that the diametric clearance is no more than 35 raicrons. 22 The apparatus is generally of stainless steel , with the piston crowns made of hardened steel. The equipment was machined and supplied by Midland Tool and Design, Birmingham, DK. The tablet is thus pushed down by the cut piston into the confines of the pocket, and comes to rest on the lower piston. The location mask and dosing sleeve and the waste film web are then removed. Second film application, cut and iron The partly enrobed core is then raised upwards within the tooling, such that half of the formed tablet sidewall is above the raised edge profile. The second film has 15gsm of glue applied to its surface via gravure roller and this is advanced over the tablets. The film is then theraoformed in the same manner as described for the first film, except that the film is held above the tablets by a spacer plate, such that the positioning of the film does not damage the top surface of the tablet. It is possible to use a lower heared platen temperature (50-150°C) for the second therrnoform, as the film is thinner and softened by Che application of glue. This helps to limit the heat exposure of the powder surface. The location mask is then positioned over the tablet and a 23 second cut piston is lowered. The second cut piston is designed such that it forms a punch cut on the outside edge of the raised edge profile of the lower tooling, with a diametric fit tolerance of no more than 25 microns. The location mask, and second cut piston and waste film web are then removed and the fully enrobed powder core is pushed through a tight fitting tablet shaped heated cylinder (40°C) to ensure the overlap seal is formed. Example 2 Same conditions as Example 1, but the following step replaces Powder dosing and film 1 cutting' stage: Powder do3inq and film 1 cutting A dosing assembly is then placed over the film formed pocket. This consists of a location mask which sits on location dowels in the platen, and a dosing sleeve that rests directly above the film formed pocket, and 3its on the raised edge profile. The dosing sleeve exactly matches the dimensions of the film formed pocket. A dose of powder is deposited into the dosing sleeve and falls into the film pocket. The cut is achieved via the cut piston that advances through the dosing sleeve and sweeps any residual powder down into the film pocket below. The level of SUBSTITUTE SHEET (RULE 26) 24 compaction is controlled by the mass of powder being deposited into the dosing 3leeve. The cutting piston cuts through the film as it interferes with the inside of the raised edge profile. The cut piston continues to engage with the raised edge for a further 1mm, and in so doing compacts the powder further into the film shell.. The fit tolerance between the cut piston and the internal dimensions of the raised edge profile are such. that the diametric clearance is no more than 25 microns. The apparatus is generally of stainless steel , with the piston crowns made of hardened steel. The equipment was machined and supplied by Midland Tool and Design, Birmingham. The tablet is thus pushed down by the cut piston into the confines of the pocket, and come3 to rest on the lower piston. The location mask and dosing sleeve and the waste film web are then removed. Example 3 Same as example 1, but the tolerance fit for the first cut piston is the same as that for the second cut piston, i.e 25 microns. SUBSTITUTE SHEET (RULE 26) 25 Exwnpla 4 Same as example 2, but the tolerance fit for the first cut piston is the same as that for the second cut: piston, i.e 25 microns. WE CLAIM : 1. A method of forming a compacted powder slug encapsulated with a film, comprising: forming a film into a pocket using vacuum and/or pressure; compacting a powder into the pocket resulting in a partially enrobed powder slug, the partially enrobed powder slug being raised above a plattcn to allow the remainder of the powder slug in said pocket to be enrobed; and enrobing the remainder of the powder slug. 2. A method as claimed in claim 1, wherein the film comprises thermoplastic material which is heated prior to being vacuum formed. 3. A method as claimed in claim 1 wherein the means for compacting the powder is mechanical. 4. A method as claimed in claim 3 wherein said mechanical means for compacting the powder utilizes one or more pistons. 5. A method of forming a compacted powder slug coated with a film, comprising vacuum forming a film into a pocket, compacting a powder to form a slug in the vacuum formed film, and vacuum forming a second film about the partially enrobed powder slug to completely coat the slug with film. 6. A method as claimed in any previous claim wherein the film has a thickness in the range between 20 and 200 microns. 7. A method as claimed in any previous claim comprising forming two separate half coatings of the film material onto the compacted powder slug. 8. A method of forming an encapsulated powder slug comprising vacuum forming a film into a pocket, compacting a powder to form a slug in the vacuum formed pocket of film to form a partially enrobed powder slug, vacuum forming a second film into a second pocket, said second vacuum formed film being introduced over the partially enrobed powder slug to completely coat the slug with film. 9. A method as claimed in claim 8 wherein the second pocket is substantially shallow. 27 10. A method of forming an encapsulated powder slug comprising vacuum forming two films into two separate pockets, compacting separate doses of powder in each pocket to form partially film coated powder slugs in each vacuum formed film pocket, bringing together same to form an encapsulated powder slug comprising two separate doses of powder. 11. A method as claimed in any previous claim whereby adhesive material is used to assist the film enrobing process. 12. A method as claimed in claim 11, comprising applying adhesive material to the surface of the compacted powder slug prior to the vacuum forming a film to completely coat the compacted powder slug. 13. A method as claimed in any one of the preceding claims wherein a plurality of powder slugs are formed simultaneously. 14. A method as claimed in any one of the preceding claims wherein a plurality of powder slugs are formed and coated substantially simultaneously. 15. A method as claimed in any one of the preceding claims wherein the powder slug is coated by films which overlap. 16. A method as claimed in claim 15, wherein the shape of slug comprises a generally cylindrical side wall portion, with two half coatings overlapping on the side wall portion. 17. A delivery capsule having an enclosing wall and powder slug core as claimed in any one of the preceding claims. 18. A delivery capsule as claimed in claim 16, whereby the films forming the enclosing wall are overlapping. 19. A delivery capsule as claimed in claim 16, wherein the delivery capsule has one or more overlapping flanges. 28 2p. A delivery capsule or method of preparing the same as claimed in any previous claim wherein the films used or the enclosing wall of the capsule, are made from a non gelatin polymeric material, modified cellulose material, starch material, modified starch material or protein films or graft copolymers of polyethylene oxide with side chains polyethylene oxide. 21. A delivery capsule or method of preparing the same as claimed in any previous claim wherein the films used or the enclosing wall of the capsule, arc made from hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC). polyvinyl alcohol (PVA). polyethylene oxide (PEO), pectin, alginate, soya or whey protein. 22. A powder slug as claimed in any one of the preceding claim. 23. A method of forming an enrobed, compacted powder slug, comprising: forming a film in a pocket, said pocket being formed by a cylinder and a piston, compacting the powder by manipulating said piston which acts in co-ordination with a second piston to compress and shape the powder into a desired slug, and enrobing the slug. 24. A method as claimed in claim 23 whereby the powder slug is coated with a film of material. 25. A powder slug as claimed in any previous claim wherein the powder slug is not a tablet. 26. A powder slug as claimed in any previous claim wherein the powder slug does not have the properties of a conventional tablet. 27. A delivery capsule comprising an enrobed, compacted powder slug, wherein films forming the enclosing walls are overlapping. 28. A method of forming a compacted powder slug encapsulated with a film, comprising: forming a film into a pocket using vacuum; compacting a powder into the pocket by mechanical means, resulting in a partially enrobed powder slug; and enrobing the remainder of the powder slug. 29. A method as claimed in claim 28 wherein said film is formed into a pocket using vacuum and pressure. 30. A method as claimed in claims 28 or 29 wherein said film enrobing the powder slug forms a skin tight wrap. 31. A method as claimed in claim 28 wherein the step of enrobing the remainder of the powder slug provides overlapping films. Powder. e.g. of a medicament, is compacted and enrobed to product compacted powder sings by preferably me charucally compating a powder and forming a film of material. prefrably hydroxy pxopyl methyl cellalose, by Vacum or pressure differintial, about the surface of the powder thus compacted.

Full Text

Powder Compaction and Enrobing
Field of the Invention
this invention concerns the compacting of powder e.g. a powder containing a medicament, vitamin, dietary supplement etc, and such compacted powder being enrobed by a biodegradable and/or water soluble film, for example a non gelatin film, such as bydroxypropyl methyl cellulose (HPMC) , to produce encapsulated bodies of compacted powder, suitable for dosage foras, e.g. for human ingestion. The invention is applicable to all related dosage forms, including tablets, but for simplicity all auch forma will be generally referred herein as capsules.
Background to the Invention
Tablets are a common type of dosage form and various means for improving their properties have been tried. Current methods for coating tablets, such as pharnaceutical tablets include the using of acelacoaters ox pan coaters. which spray low molecular weight HPMC grades onto tablets so iaparting a surface layer, which as uniform and smooth, but opaque and of low gloss. It is possible for the tablets to have embossed lettering on them. This method of coating tablets is however very time consuming and requires a high level of expertise to produce satisfactory results. Production complications such
SUBSTITUTE SHEET (RULE 26)

2
as tablet twinning are common, where two tablets becone attached to one another during the spray coating operation. In addition to thQso problems it is necessary to compact the tablets under relatively high pressures so that they do not disintegrate during the coating process. This high level of compaction can have an adverse effect on the disintegration and dissolution rates of active ingredients contained within the capsule, for example, leading to a delay in the release of a drug to a patient, whilst the tablet slowly dissolves in the stomach of the patient.
An alternative Co spray or pan coating is to use two-piece hard capsules. These are produced by a dipping process, typically a HPMC solution is used, producing half shells which interlock and thus produce an enclosed capsule. These capsules are typically opaque but glossy, and cannot have any form of embossment, as this would interfere with the overlap interlocking process. The nature of the capsule dictates that there will always be an airspace above the powder fill level. Additionally, it ia not possible to compact the powder .into these tablets, and this so limits the quantity of powder which can be encapsulated. It follows that this lack of compaction can effectively reduce the amount of e.g. medicament which can be encapsulated. The existence of the air space in the capsule and lack of compaction of the powder contained within the capsule leads to a capsule that 13 inevitably larger than necessary.
SUBSTITUTE SHEET (RULE 26)

It has also been found that, after manufacture and/or' sale of two-piece hard capsule3, the capsules can be easily and illegally interfered with, as it is possible to separate the two halves of the capsule and tamper with its contents and replace the two halves back together without there being any obvious change in the capsule's external appearance such to suggest to the user that there was anything wrong with the capsule. This means that it can be difficult to detect capsules which have had their contents tampered with. KPMC and certain other non-gelatin materials are suitable for ingestion by humans, so delivery capsules with gelatin walls find potential use as ingestible capsules, e.g. for the delivery of accurately metered doses of pharmaceutical preparations and dietary supplements, AS a possible replacement for gelatin based capsules. Conventional tablets have already been enrobed. See for example WO 02/098394.
Summary of the Invention
One aspect of the invention concerns a novel method for
compacting and enrobing a powder to produce capsules with
enhanced properties.
A non gelatin film layer is thermo.foxmed into a suitable
tablet shaped pocket under the influence of heac and/or
vacuum, and/or pressure. A pre-determined mass of powder is
dosed into the film formed pocket, and compressed into a
SUBSTITUTE SHEET (RULE 26)

4
tablet shape e.g. with the aid of a piston or pistons. A partially enrobed 'soft' tablet results from this process, which is then fully enrobed by a second sequence of events which involves the raising of the tablet above a platten which allows the remainder of the compressed tablet to be enrobed by a second film. Suitable tablet shaped pockets can be created by using e.g. a pair of pistons slideable within a cylinder, such pistons also having the advantage of being able to form pinch points between the platen and the top of cylinders which are useful for cutting away unwanted excess film from the (partially) enrobed tablets.
One of the aims of "the present invention is to produce taaper evident capsules.
Another aim of the present invention is to produce powder filled capsules whereby the powder is enrobed with a material which may or may not form a skin tight wrap'.
Another aim of the present invention is to produce a capsule
with a high gloss surface which is able to adopt an
underlying embossment, e.g. to identify a pharmaceutical
tablet.
Another aim of the present invention is to produce capsules which have a flange which is almost non-discernable.
SUBSTITUTE SHEET (RULE 26}

5
Another aim of the present invention is to enable the' production of dosage forms in a wide variety of shapes and sizes, which , because of the nature of the processes involved and the properties of the product produced, includes shapes and sizes of dosage forms which have not been previously possible to make or practical to use.
Another aim of the present invention is to produce capsules with favourable properties and which contain powd.es or other flowable solid material which is at a favourable state of compaction and/or composition, and/or the encapsulating medium of the capsule being fast dissolving or dissolvable(with control) pharmaceutical grade films plasticised with pharmaceutical grade materials.
Another aim of the present invention is to produce capsules, which by their nature, are easy to swallow, and more easily can be conveyed to the site where it is desirable where tne active ingredients are most advantageously released.
Another aspect the present invention is a method of powder compaction to produce powder compacted slugs, which , for example can be enrobed to produce capsules which possess enhanced disintegration and dissolution properties over and above traditional tablets.
SUBSTITUTE SHEET (RULE 26)

Another aspect of the present invention is a method of producing a capsule, which, at the very least can perform the same function as * conventional coated tablet, but in which the conventional tablet pressing and coating stages are replaced by a single powder enrobing process.
Another aspect of the present invention is a method of producing a capsule by enrobing powder, in which, because of the nature of capsule produced, certain ancillary ingredients necessary in conventional tablet production, can be omitted. For example, ingredients in a tablet which are added to give the tablet its structural integrity can be omitted, because the active ingredients are in powder form, relatively loosely compacted are encapsulated within a film, such film which now securely packages the powder/ ingredients, thus giving integrity and forming a discrete effective dosage form. Because of the aforementioned, components contained within a tablet which are designed to disperse and break up the tablet when it has reached the site of delivery, can be omitted, as the active ingredients in the capsule according to the present invention arts in a non-compacted or at least less compacted form as compared to a conventional tablet, and this lesser compaction leads to the easy release and dispersal of active ingredients once the capsule film has dissolved, e.g-at the. intended site of delivery.
SUBSTITUTE SHEET (RULE 26)

7
Another aspect of the invention provides a method of enrobing compacted powder, comprising vacuum forming a film into a pocket, compacting a powder in said pocket, resulting in a partially enrobed powder slug in a pocket. Vacuum forming a second film over this powder slug to completely enrobe the powder slug, forms a discrete compacted powder filled capsule, suitable for use as a dosage form.
In yet another aspect of the present invention provides a method of enrobing compacted powder using film or films, to form a compacted powder filled capsule, wherein the film or films forming the wall of the compacted powder filled capsule used overlap each other.
In a further aspect of the pxesent invention provides a method of forming and/or enrobing a compacted slug wherein the level of compaction of the compacted powder is less than that necessary to reach the industry standard for the discrete slug of compacted powder to be described as a tablet.
In practising the method of the invention, the films are caused to deform to conform with the external surface of the pocket and the compacted powder slug, the films effectively forming a secure capsule, by being wrapped around the powder slug, vacuum chamber or vacuum bed apparatus, in which the films and powder are located in a suitably shaped support and
SUBSTITUTE SHEET (RULE 26)

8
exposed to conditions of vacuum (or substantially reduced pressure) can be modified and used for this purpose. 'Such apparatus may be based on commercially available vacuum chamber or vacuum bed apparatus, suitably modified- Vacuum forming techniques result in the compacted powder being completely enclosed and encapsulated within a film, leading to a capsule containing compacted powder, such capsule having enhanced and controllable properties over dosage forms currently available, such as conventional tablets. The powders to be compacted are typically.subjected to pressures between, but not limited to, 5-15 mega pascals. Examples of powders compacted and enrobed include paracetamol, ibuprofen, sorbitol and multivitamin. Other powder fill3 which are contemplated are antacid, anti-inflammatory, anti-histamine antibiotic and anti-cholesterol drugs.
The film should be a material which is suitable for human consumption end that has sufficient flexibility and plasticity to be vacuum formable. Some film materials have suitable properties in their natural condition, but commonly it will be necessary to pre-treat the film material so that it is vacuum formable. For example, it may be necessary to expose the film material to a solvent therefor; for instance certain grades of polyvinyl alcohol (PVA) will vacuum, form after application of a small amount of water to the surface thereof or when exposed to conditions of high humidity. A
SUBSTITUTE SHEET (RULE 26)

9
further generally preferred possibility, is to use a film of thermoplastic material (i.e. material capable of deforming plastically on Seating) with the film to be in heat-softened condition prior to being thennoformed by exposure to vacuum-Suitable thermoplastic materials include modified cellulose materials, particularly hydroxypropyl methyl cellulose (HPMCJ and hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA) , polyethylene oxide (PEO) , pectin, alginate, starches, and modified starches, and also protein films such as soya and whey protein films. The currently preferred film material ia HPMC. Suitable film materials are currently available.
When using thermoplastic film, the film as typically heated prior to application to pocket or compacted powder slug, so that the film is in a heat softened deformable condition. This can be achieved by exposing the film to a source of heat e.g. an infrared heater, infrared lamps, a heated plate a hot air source etc. In the process described, a range of temperatures may be used, but by way of example only, whore films of different thickness may bo utilized for the first and second films in the process, a first film forming temperature of around 150 degrees centigrade may be used and for the second film forming stage, a range of approximately 70-80 degrees centigrade may be used.
SUBSTITUTE SHEET (RULE 26)

10
During the enrobing process, films may be caused to overlap, preferably a minimum of 1.5mm-2mm. Compacted powder slugs may preferably have a sidewall height of about 3mm and films may be caused to overlap substantially completely over the sidewall area.
The film material may include optional colourings, e.g. in the form of food dyes auch as FD and C yellow number S, and/or optional flavourings, e.g. sweeteners, and/or optional textures etc in known manner.
The film material typically includes plasticiscr to give desired properties of flexibility to the film in known manner. Materials used as plastlcisers include alpha hydroxy acids such as lactic acid and salts thereof, roaleic acid, benzyl alcohol, certain iactones, diacetin, triacetin, propylene glycol, glycerin or mixtures thereof. A typical thermoplastic film formulation is HPMC 77 by weight, plasticiser 231 by weight.
The film suitably his a thickness in the range 20-200 microns, conveniently 50 to 100 microns, e.g. at about 80 microns, with appropriate film thickness depending on factors including the size and form of the tablet. Films of different thickness may be used, e.g. a film of greater thickness may be used in the first stage of the enrobing process, say 125
SUBSTITUTE SHEET (RULE 26)

11
microns thickness and a film of lesser thickness may be used in the second stage of the enrobing process, say 80 microns thickness.
Because of the nature of the film forming process according to the present invention, under certain circumstances, e.g. where the powder to be compacted contains particles which, under compaction, have the ability to pierce film, it may be advantageous to have the thickness of the film formed in the pocket to be greater than, that of the film which is to cover the remainder of the compacted powder slug {in the second ant final phase of enrobement of the compacted powder). Such differential thickness may give rise to certain advantageous structural features of the resultant capsule; the capsule my be generally more robust and 30 may be more safely stored and handled I generally thicker film on the capsule ), but such cap9ule also possessing a smaller araa (window} of weaker, thinner film which can give rise to quicker release characteristics by the thinner film will dissolving more quickly when exposed to any given solvent. An advantageous differencial film thickness to form a capsule with wall of different thickness, could be e.g. 70/90 micron film coordination to produce cap3ules which are robust but which release their contents caiickly, through a window of thinner film.
Therefore films of different thickness may be used in the enrobing process, and to give a further examples, a film of
SUBSTITUTE SHEET (RULE 26)

12
greater thickness may be used in the first stage of the enrobing process, a maximun of 200 microns and a minimum of 70 microns but say preferably 125 microns thickness and a film of lesser thickness may be used in the second stage of the enrobing process, a maximum of 125 nicrons and a mlninun of 50 microns, but say preferably 80 microns thickness. Wben making multiples of enrobed compacted powder slugs , the spciog of the compacted powder slugs can be important. If the compacted powder slugs are position ed too closely together, the film is not able to fully thermoform between them. For example, a spacing between the adjacent compacted powder slugs of about 4mm has been found to give good results, the film being able to fully adopt the vertical sidewall of the compacted powder slug to a distance of about 2mm before it begins to curve away from the side of the compacted powder slug.
According to one aspect of the invention , the method involves forming two separate overlapping half coatings of film, effectively on the compacted powder slug. The method preferably involves, first forming a film in a pocket, then compacting a powder slug into the film lined pocket, thereby effectively coating/encapsulating a substantial portion of a
SUBSTITUTE SHEET (RULE 26)

13
powder slug within a film formed into a partial capsule, removing tbe regaining film material not coating the' compacted powder slug e.g. by cutting, then coating the remaining half of the compacted powder slug, with overlapping portions of the two coatings sealed together to provide a 3ealed complete enclosure for the slug, and again removing remaining surplus film material not coated on the slug. It may be necessary to apply adhesive material between the overlapping film coatings e.g. to the surface of the film layers, to ensure the formation of an effective seal therebetween and to make the resultant capsule tamper-evident. The adhesive material conveniently has the same composition as the film, but with a greater proportion of plasticiser, e.g. 93% to 98% by weight plasticiser, so as to provide a less viscous material. The adhesive material may be applied, e.g. by use of a roller, spraying etc. A typical adhesive fonr.ulation, with & representing % by weight, is HPMC 4%, lactic acid 77%, water 19%.
The compacted powder slug and capsule conveniently include a generally cylindrical side wall portion, with two half coatings overlapping on this side wall. Tablets of circular symmetrical form with a circular cylindrical side wall are very common, but other forms e.g. generally oblong and oval, again including a generally cylindrical side wall, are also Known.
SUBSTITUTE SHEET (RULE 26)

14
It nay be also advantageous or desirable to apply adhesive material e.g. as described above, to the surface of compacted powder slug prior to the final stage of coating, to promote adhesion of the second portion of the film thereto. Again, this may be achieved by e.g. use of a roller, spraying etc.
A plurality of tablets in an array may be conveniently coated simultaneously, using a suitably large sheet of film material.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
This invention is now further described in detail, by way of example only, with reference to the drawings. Steps a-k show the basic compaction and enrobing apparatus and process.
The drawings show the various stages of a powder compaction/enrobing process.
Figure 1 shows the mechanism of the basic steps of powder compaction and entoboraent: via steps a-1:
a. A first film (1) is laid upon a platten (2). Lower
piston (3), slideable in cylinder (4) incorporates
vacuum port (5).
b. Film (1) completely drawn down into cylinder (4) by a
vacuum created by vacuum port (5) and said film (l) also
SUBSTITUTE SHEET (RULE 26)

15
resting on the crown of lower piston (3), to form a pocket shape.
c. A quantity of powder (6) is introduced over the pocket
of film and upper piston (9) moves downward towards the
lower piston (3) compressing a quantity of powder {€)
d. A compacted powder slug (7) resulting from the
completion of step c.
e. Cutting of film by the introduction of cutting tool (10)
to torm an isolated semi enrobed slug of compacted
powder.
f. Lower piston (3) begins to move upwards, thereby also
urging compacted powder slug (7) upwards.
g. Lower piston (3) comes to rest, positioning compacted
powder slug (7) proud of platen (2)
h. Introduction of a second film (8) over platen (2)and also loosely stretching over compacted powder slug (7)
i. Second vacuum is applied drawing second film (8) around and closely in association with the upper portion of compacted powder slug (7), second film {8) thereby wrapping itself around the upper part of the compacted powder slug (7).
j. Cutting tool (12) descending and trimming off excess unwrapped film from powder slug (7).
k. Fully enrobed powder slug, has been ejected from cylinder(4)by the further upward movement of lower piston (3) and has the loose ends of the films ironed and sealed by irons (13) .
SUBSTITUTE SHEET (RULE 26)

1. Shows a fully enrobed tablet with ironed seams.
Figure 2 depicts a variation of the basic process described by figure 1.
Steps al and bl show a second pre-forned film pocket, formed by a second vacuum forming pocket (14) being lowered onto the platten immediately above a partially enrobed powder slug as shown in step f of figure 1. Once the opposing film pocket is in position lower piston (3) moves upwards thus pushing compacted partially enrobed powder slug also upwards and into the cavity of the second pre-formed film pocket, thus capping the partially enrobed powder slug to form a fully enrobed capsule, enrobed by two pockets of film. The capsule is then released , trimmed and ironed as mentioned previously.
Figure 3 depicts a further variation of the basic process described by figure 1.
Step a2 shows a powder slug as in step f of figure l, and Like figure 2 a second pre-formed film pocket is introduced, but this time it is a shallow pocket, forced by a second shallow vacuum forming pocket (15), such to only coat the top of the powder slug and to form a. seal at the circumference of ths very edge of the cylindrical
SUBSTITUTE SHEET (RULE 26)

17
portion of the powder slug. Steps a2-d2 show this revised process. This process gives rise to a capsule with a different type of seal which gives rise to different properties in the capsule.
Figure 4 depicts another variation of the process described by figure 1.
However the basic process is essentially duplicated to form a capsule which contains two distinct half doses of powder. The basic process as described in figure ) is carried out up to step f, in duplicate, which is basically steps a3-c3 in figure 4. The main differences at this point in figure 4, are that the two opposing pockets filled vith compacted powder (16,17) ate half size in depth, and the top of the powder slugs are essentially flat, rather than rounded. Step c3 may include the laying down of an intermediate film on the surface of the half slug. Steps d3-f3 show the bringing together of 2 half slugs to form a single capsule, comprised of 2 parts Step q3 shows a compartmentalized capsule. The advantages ace at least 2 separate doses of active ingredients can be incorporated into 1 capsule, under pechaps different compaction pressures etc. This gives rise to further flexibility and options as to the performance of the new dosage forms.

18
The process described, and in conjunction with the quantity of powder used, with the careful positioning of the co-acting pistons during the compaction process/ can facilitate the formation of powder slugs having various levels of compaction. As previously described, these varying levels of compaction are allowed in the powder slugs because the slugs are enrobed within a film, and it is this film enrobement which provides the slug with the necessary integrity it needs so that it can function as a convenient and stable dosage form. The process and apparatus can be modified such to produce capsules with varying properties, which have advantages over tablets and conventional capsules already known in the art. For exanple, a capsule according to the present invention containing a powder with a low compaction, could produce extremely favourable quick release characteristics, suitable, e.g. for a fast acting analgesic; the film can be both designed to be smooth/flexible, to allow the capsule to quickly and relatively painlessly travel to the intended site of drug delivery through the digestive tract, and also be designed to dissolve at or neax the intended site of drug delivery. The lower compaction of the powder in the capsule can also aid smooth travel of the capsule in the digestive tract, as the contents of the capsule can be designed to be compressible and mobile, thus

19
allowing the capsule to be bent and/or compressed as it travels through the body so that it can conform to th'e 3hape of a more restricted part of a. passage, squeeze through it and so continue its journey through the digestive tract with leas hindrance. Such dosage forms may find themselves especially useful where a patient finds difficulty in swallowing, has a painful or restricted digestive tract, or there is some ether reason why a dosage form is required to be more mobile and less aggressive to the internals of the body.
The following methods are given by way of example and it is not intended to limit the invention in any way:
Example 1
Consumable items:
Film 1 - 125micron thickness, hpmc plasticised with lactic
acid 15%, and triacetin 5%, processing aids starch 1% and
aorbitol monostearate 0.25%.
Film 2 as film 1 but 80 micron thickness.
Glue applied to overlap area of first film - benzyl alcohol
45$, triacetin 50%,hpmc El5 Premium (Dow Chemical Corp.) 5%
SUBSTITUTE SHEET (RULE 26)

20 Process description
Film 1 is thermofonned into single or multiple tablet/caplet shaped pockets m a platen, each pocket containing a lower piston that can be raised or lowered as necessary to suit standard sized tablets and caplets. The tablet shaped pocket also has a raised edge profile around the top perimeter of the pocket. Thi3 edge profile is raised Irani above the platen surface and has a land width of 0.35mm. The vertical sidewall of these pockets is typically 3niin deep.
The thermoforming operation involves the film acting as a membrane dividing the two halves of a vacuum chamber, which are separately controlled. . The chamber above the film contains a flat heated platen at a temperature of approximately 150°C. Vacuum is drawn above the film causing it to be held against the heated plate for a period of 1 to 5 seconds preferably 3 seconds. The vacuum xn the upper chamber is maintained whilst vacuum is also applied to the lower chamber. At this stage the film remains against the heated platen. Once the vacuum level in the lower chajnber reaches at least -0.65 bar the vacuum in the upper chamber is released to atmosphere or replaced by positive pressure, this forces the film downwards away from the heated platen and onto the tablet pocket shaped tooling below. In this way the film adopts the shape of the tablet pockets in the lower tooling.
SUBSTITUTE SHEET (RULE 26)

*1
Powder dosing and film 1 cutting
A dosing assembly is then placed over the film formed pocket. This consists of a location mask which sits on location dowels in the platen, and a dosing sleeve that rests directly above the film formed pocket, and aits on the raised edge profile. The dosing sleeve exactly matches the dimensions of the film formed pocket. A dose of powder is deposited into the dosing sleeve and falls into the film pocket. Compaction is achieved via a compaction piston that advances through the dosing sleeve and sweeps any residual powder down into the film pocket below and compacts it to a fixed
stop, such that it does not cut the film, but instead comes to rest, directly adjacent to the film. The level of compaction is controlled by the mass of powder being deposited into the dosing sleeve. The piston below the compacted powder tablet is then lowered and either the compaction piston is advanced by a similar amount causing a punch cut through the film as it interferes with the inside or the raised edge profile. Alternatively the compaction piston is replaced by a cut piston which similarly advances and causes a punch cut with the raised edge profile. The fit tolerance between the cut piston and the internal dimensions of the raised edgs profile are such that the diametric clearance is no more than 35 raicrons.

22
The apparatus is generally of stainless steel , with the piston crowns made of hardened steel. The equipment was machined and supplied by Midland Tool and Design, Birmingham, DK.
The tablet is thus pushed down by the cut piston into the confines of the pocket, and comes to rest on the lower piston. The location mask and dosing sleeve and the waste film web are then removed.
Second film application, cut and iron
The partly enrobed core is then raised upwards within the tooling, such that half of the formed tablet sidewall is above the raised edge profile. The second film has 15gsm of glue applied to its surface via gravure roller and this is advanced over the tablets. The film is then theraoformed in the same manner as described for the first film, except that the film is held above the tablets by a spacer plate, such that the positioning of the film does not damage the top surface of the tablet. It is possible to use a lower heared platen temperature (50-150°C) for the second therrnoform, as the
film is thinner and softened by Che application of glue. This helps to limit the heat exposure of the powder surface. The location mask is then positioned over the tablet and a

23
second cut piston is lowered. The second cut piston is designed such that it forms a punch cut on the outside edge of the raised edge profile of the lower tooling, with a diametric fit tolerance of no more than 25 microns. The location mask, and second cut piston and waste film web are then removed and the fully enrobed powder core is pushed through a tight fitting tablet shaped heated cylinder (40°C) to ensure the overlap seal is formed.
Example 2
Same conditions as Example 1, but the following step replaces Powder dosing and film 1 cutting' stage:
Powder do3inq and film 1 cutting
A dosing assembly is then placed over the film formed pocket. This consists of a location mask which sits on location dowels in the platen, and a dosing sleeve that rests directly above the film formed pocket, and 3its on the raised edge profile. The dosing sleeve exactly matches the dimensions of the film formed pocket. A dose of powder is deposited into the dosing sleeve and falls into the film pocket. The cut is achieved via the cut piston that advances through the dosing sleeve and sweeps any residual powder down into the film pocket below. The level of
SUBSTITUTE SHEET (RULE 26)

24
compaction is
controlled by the mass of powder being deposited into the dosing 3leeve. The cutting piston cuts through the film as it interferes with the inside of the raised edge profile. The cut piston continues to engage with the raised edge for a further 1mm, and in so doing compacts the powder further into the film shell.. The fit tolerance between the cut piston and the internal dimensions of the raised edge profile are such. that the diametric clearance is no more than 25 microns.
The apparatus is generally of stainless steel , with the piston crowns made of hardened steel. The equipment was machined and supplied by Midland Tool and Design, Birmingham.
The tablet is thus pushed down by the cut piston into the confines of the pocket, and come3 to rest on the lower piston. The location mask and dosing sleeve and the waste film web are then removed.
Example 3
Same as example 1, but the tolerance fit for the first cut piston is the same as that for the second cut piston, i.e 25 microns.
SUBSTITUTE SHEET (RULE 26)

25
Exwnpla 4
Same as example 2, but the tolerance fit for the first cut piston is the same as that for the second cut: piston, i.e 25 microns.

WE CLAIM :
1. A method of forming a compacted powder slug encapsulated with a film, comprising:
forming a film into a pocket using vacuum and/or pressure;
compacting a powder into the pocket resulting in a partially enrobed powder slug, the partially enrobed powder slug being raised above a plattcn to allow the remainder of the powder slug in said pocket to be enrobed; and
enrobing the remainder of the powder slug.
2. A method as claimed in claim 1, wherein the film comprises thermoplastic material
which is heated prior to being vacuum formed.
3. A method as claimed in claim 1 wherein the means for compacting the powder is
mechanical.
4. A method as claimed in claim 3 wherein said mechanical means for compacting the
powder utilizes one or more pistons.
5. A method of forming a compacted powder slug coated with a film, comprising
vacuum forming a film into a pocket, compacting a powder to form a slug in the
vacuum formed film, and vacuum forming a second film about the partially enrobed
powder slug to completely coat the slug with film.
6. A method as claimed in any previous claim wherein the film has a thickness in the
range between 20 and 200 microns.
7. A method as claimed in any previous claim comprising forming two separate half
coatings of the film material onto the compacted powder slug.
8. A method of forming an encapsulated powder slug comprising vacuum forming a film
into a pocket, compacting a powder to form a slug in the vacuum formed pocket of
film to form a partially enrobed powder slug, vacuum forming a second film into a
second pocket, said second vacuum formed film being introduced over the partially
enrobed powder slug to completely coat the slug with film.
9. A method as claimed in claim 8 wherein the second pocket is substantially shallow.

27
10. A method of forming an encapsulated powder slug comprising vacuum forming two
films into two separate pockets, compacting separate doses of powder in each pocket
to form partially film coated powder slugs in each vacuum formed film pocket,
bringing together same to form an encapsulated powder slug comprising two separate
doses of powder.
11. A method as claimed in any previous claim whereby adhesive material is used to
assist the film enrobing process.
12. A method as claimed in claim 11, comprising applying adhesive material to the
surface of the compacted powder slug prior to the vacuum forming a film to
completely coat the compacted powder slug.
13. A method as claimed in any one of the preceding claims wherein a plurality of
powder slugs are formed simultaneously.
14. A method as claimed in any one of the preceding claims wherein a plurality of
powder slugs are formed and coated substantially simultaneously.
15. A method as claimed in any one of the preceding claims wherein the powder slug
is coated by films which overlap.
16. A method as claimed in claim 15, wherein the shape of slug comprises a generally
cylindrical side wall portion, with two half coatings overlapping on the side wall
portion.
17. A delivery capsule having an enclosing wall and powder slug core as claimed in any
one of the preceding claims.
18. A delivery capsule as claimed in claim 16, whereby the films forming the enclosing
wall are overlapping.
19. A delivery capsule as claimed in claim 16, wherein the delivery capsule has one or
more overlapping flanges.

28
2p. A delivery capsule or method of preparing the same as claimed in any previous claim wherein the films used or the enclosing wall of the capsule, are made from a non gelatin polymeric material, modified cellulose material, starch material, modified starch material or protein films or graft copolymers of polyethylene oxide with side chains polyethylene oxide.
21. A delivery capsule or method of preparing the same as claimed in any previous claim
wherein the films used or the enclosing wall of the capsule, arc made from
hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC). polyvinyl
alcohol (PVA). polyethylene oxide (PEO), pectin, alginate, soya or whey protein.
22. A powder slug as claimed in any one of the preceding claim.
23. A method of forming an enrobed, compacted powder slug, comprising:
forming a film in a pocket, said pocket being formed by a cylinder and a piston, compacting the powder by manipulating said piston which acts in co-ordination with a second piston to compress and shape the powder into a desired slug, and
enrobing the slug.
24. A method as claimed in claim 23 whereby the powder slug is coated with a film of
material.
25. A powder slug as claimed in any previous claim wherein the powder slug is not a
tablet.
26. A powder slug as claimed in any previous claim wherein the powder slug does not
have the properties of a conventional tablet.
27. A delivery capsule comprising an enrobed, compacted powder slug, wherein films
forming the enclosing walls are overlapping.
28. A method of forming a compacted powder slug encapsulated with a film, comprising:
forming a film into a pocket using vacuum;
compacting a powder into the pocket by mechanical means, resulting in a partially enrobed powder slug; and
enrobing the remainder of the powder slug.

29. A method as claimed in claim 28 wherein said film is formed into a pocket using vacuum and pressure.
30. A method as claimed in claims 28 or 29 wherein said film enrobing the powder slug
forms a skin tight wrap.
31. A method as claimed in claim 28 wherein the step of enrobing the remainder of the
powder slug provides overlapping films.
Powder. e.g. of a medicament, is compacted and enrobed to product compacted powder sings by preferably me charucally compating a powder and forming a film of material. prefrably hydroxy pxopyl methyl cellalose, by Vacum or pressure differintial, about the surface of the powder thus compacted.

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Patent Number

206580

Indian Patent Application Number

01747/KOLNP/2004

PG Journal Number

18/2007

Publication Date

04-May-2007

Grant Date

03-May-2007

Date of Filing

18-Nov-2004

Name of Patentee

BIOPROGRESS TECHNOLOGY INTERNATIONAL, INC.

Applicant Address

9055 HUNTCLIFF TRACE, ATLANTA,GA 30350

Inventors:

#	Inventor's Name	Inventor's Address
1	KESSEL STEPHEN RONALD	9 HIGH STREET, WARBOYS CAMBRIDGESHIRE PE28 2RH
2	TECKOE JASON	23 WEST END,ELY ,CAMBRIDGESHIRE CB6 3AY

PCT International Classification Number

A 61 J 3/10

PCT International Application Number

PCT/GB03/02145

PCT International Filing date

2003-05-19

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	0211620.0	2002-05-21	U.K.