Title of Invention

A PROCESS FOR OBTAINING A SOLID ORGANIC MATERIAL OF DESIRED SHAPE AND SIZE

Abstract

The present invention relates to a process to obtain a solid organic material of a desired shape by a) heating a solid organic material to a temperature that is not higher than 4 degrees centigrade below the melting temperature of the organic material for a specified period of time b) extruding the organic material c) preferably merumerising or spherodising the material to a desired shape and size. Optionally, other organic or inorganic materials may be added during any step of the process.

Full Text

FORM -2 THE PATENTS ACT, 1970 (39 OF 1970) COMPLETE SPECIFICATION (See Section 10; rule 13) A PROCESS FOR OBTAINING A SOLID ORGANIC MATERIAL OF DESIRED SHAPE AND SIZE (2) HINDUSTAN LEVER LIMITED, a company incorporated under the Indian Companies Act, 1913 and having its registered office at Hindustan Lever House, 165-166 Backbay Reclamation, Mumbai 400 020, Maharashtra, India The following specification particularly describes the nature of this invention and the manner in which it is to be performed. TECHNICAL FIELD The present invention relates to a process for obtaining a solid organic material of desired shape and size. The granulation of an organic solid material is done using minimal or no agglomeration aids. In particular, the invention relates to the granulation of castor oil and/or ricinoleic acid derivatives to obtain substantially spherical material. BACKGROUND TO THE INVENTION Organic solids, like castor oil or ricinoleic acid derivatives are used in several formulations. The solids are usually available in the form of flakes. They have a wide distribution of shape and size and there are inherent problems associated with the currently available material like 1) the tendency of flakes to adhere together and form lumps of undesired shape and size causing poor flow properties 2) dusting 3) inefficient packing due to the low bulk density of the materials and 4) cumbersome handling as the materials cannot be easily conveyed pneumatically. Granulation is a process whereby the size of small or fine particles is increased to particles of larger size . By granulation, the material can be obtained in a convenient form like spheroid, cylindrical, irregular bound aggregates etc. Granulation of a material overcomes disadvantages like difficulties in storage and packing, poor flow properties and cumbersome handling amongst others. Dry and wet granulation methods including compaction, extrusion, agitation and fusion are known in the art and can be applied to organic and inorganic materials. Most granulation processes require the use of a binder or additives. Binders provide the 'cohesiveness' to the material enhancing its compressibility and flow properties. Granulation is a well known technique in the pharmaceutical industry. The drug is admixed with other ingredients to form a tablet or granule by methods like compression, agitation granulation, tumbling granulation, stirring granulation, extrusion granulation etc. When organic solids like hardened castor oil are used as binders in such granulation processes, the granulation is carried out at a temperature above the melting point of the binder. Thus, WO0000179 (Won Jin Biopharma Co., Ltd.) relates to solid dispersed preparations for poorly water-soluble drugs. The drug is dissolved or dispersed in an oil, a fatty acid or a mixture thereof, the solution or dispersion is mixed with a water-soluble polyol matrix followed by drying the mixture and pulverizing the dried mixture to give a dispersed powder. The drying is done so as to give a dispersed granular preparation. Hydrogenated castor oil can be used as an oil for dissolving the drug. JP08053357 (OTA SEIYAKU KK FUJI CHEM IND CO LTD) relates to a fast-soluble sodium alginate solid preparation for oral administration. The solid material is prepared by subjecting sodium alginate powder to stirring granulation or an extrusion granulation to form into granules in the presence of an alcoholic aqueous solution containing one or more kinds of surfactants selected from a sucrose fatty acid ester, a sorbitan fatty acid ester, a glycerol fatty acid ester, a polyoxyethylene sorbitan fatty acid ester, a polyglycerol fatty acid es.ter, a polyoxyethylene hardened castor oil and lecithin compounds in an amount of 0.1-5.0 wt.% based on the whole weight. The prior art as disclosed is therefore principally directed towards the use of organic solids like castor derivatives as binders for granulation of other materials. The process is also typically carried out at a temperature above the melting temperature of the organic solid like the castor derivative. US5019302 (Washington University Technology Associates, Inc.) discloses a process for granulation of a powdery material requiring partial or complete melting of the material to be granulated. A binder may also be added. Granulation is achieved by centrifugally spreading out the powder over a heated disk or bowl, conveying the partially liquid film that is so formed to the edge of the disk or bowl by centrifugal action, allowing rapid solidification at the edges. The process is achieved in a short time. The invention is particularly directed towards the granulation of organic drugs like acetaminophen. It is required that at least part of the material be heated to above its melting point. However, US 5019032 does not address the problem of granulating the organic solid to a required shape and size by a suitable simple method of processing. The processing method as disclosed requires a control over temperature in order to prevent undesirable temperature changes that may cause decomposition or degradation of the material to be granulated. This is achieved by controlling air currents above the spreader and below the spreader by means of baffles, screen etc. Also, a number of parameters like size and configuration, speed of rotation, temperature, use and control of baffle means need to be adjusted in order to obtain the granulated material having the desired characteristics. This renders the process tedious and cumbersome. Another drawback of the invention as disclosed is that the process does not provide for a uniform size distribution as control of particle size is difficult to achieve. Further, ungranulated material is present in the final product. While extrusion is an advantageous technique for granulation, organic solids themselves cannot be readily granulated by using extrusion. This is because physical compaction is not sufficient to provide strength to the granule. It is found, for example, that if an organic solid is extruded, then the extrudate does not form a cohesive mass and the granule, if formed, disintegrates at the application of a small force. Melting the organic solid would also make extrusion difficult. Thus the prior art does not provide for a simple, inexpensive method of extrusion granulation that gives granulated material of uniform size distribution and desired shape. Also, a technique of granulation wherein neither the organic material nor the binder is melted is hitherto unknown in the art. Melting or partial melting of one of the granule components is essential to achieve agglomeration. The present applicants have now found that granulated organic solids of a desired shape containing minimal or no agglomeration aids and having advantageous properties like good flow properties, no dusting, easy packing and being able to be conveyed pneumatically can be obtained by heating the organic solid to a temperature below the melting temperature of the organic solid for a specified period of time, followed by extrusion at a temperature below the melting temperature of the organic solid, followed by an optional step of shaping the granules to a required shape. The process gives solid organic material of a desired shape and also gives organic solids with a narrow particle size distribution and high bulk density Such processes can be applied to any organic solid, in particular to derivatives of castor oil and/or ricinoleic acid. DETAILED DESCRIPTION OF THE INVENTION All parts herein are by weight unless otherwise mentioned in the text. By the term solid organic material is meant both a single material or a mixture of organic materials which together form a solid. The invention provides provides a process for obtaining a solid organic material of desired shape and size comprising the steps of: a) heating the solid organic material to a temperature below the melting temperature of the organic material for at least 5 minutes b) extruding the solid organic material at a temperature below the melting temperature of the organic material and optionally cutting the extrudate c) preferably smoothening or providing a substantially spherical shape to the extruded material by merumerisation or spherodisation. Preferably the organic material is heated and extruded at a temperature which is not higher than 4° below the melting point. According to a preferred aspect the invention provides a process for obtaining a castor oil and/or ricinoleic acid derivative of desired shape and size comprising the steps of: a) heating the castor oil and/or ricinoleic acid derivative to a temperature below the melting temperature of the organic material for at least 5 minutes b) extruding the castor oil and/or ricinoleic acid derivative at a temperature of at or above its softening temperature and below its melting temperature c) preferably smoothening or providing a substantially spherical shape to the extruded material by merumerisation or spherodisation. Especially preferred castor oil derivatives are 12 hydroxy stearic acid and hydrogenated castor oil. Optionally, other organic and inorganic materials may be added at any step of the process provided they are not greater than 10% of the final granulated material. The materials can be in liquid or solid form. Using the process of the invention, granules of selective shape and size can be obtained. The bulk density of the organic material can also be increased thus overcoming problems of packing during transportation. Dusting is reduced and it is possible to pneumatically convey the granulated material. The process of the invention is particularly suitable for castor oil and/or ricinoleic acid derivatives. THE PROCESS The heating step can be carried out by any conventional means by using direct or indirect thermal energy by convective and conducting mode of heat transfer. For example, heating can be carried out on a tray that is provided with a temperature controller. The material is heated to a temperature at least 4 degrees centigrade below the melting temperature of the organic material and preferably not less than 25 degrees centigrade below the melting temperature of the organic material. The time required for heating will be dependent on the thermal gradient as well as the nature of the solid organic material. When a castor oil and/or ricinoleic acid derivative is heated its is conveniently heated at a temperature of from 45 degrees centrigrade to 90 degrees centrigrade, provided the limit of 4° below the melting temperature of the material is not exceeded. Preferably the heating is carried out for a period of 12 to 35 minutes. 12-hydroxy stearic acid and hydrogenated castor oil are especially preferred castor oil derivatives. When 12-hydroxy stearic acid is the solid organic material, the heating is suitably carried out at a temperature of from 50 degrees centrigrade to 55 degrees centrigrade for a period of 12-35 minutes in a suitable heater. When hydrogenated castor oil is the solid organic material, the heating is suitably carried out at a temperature of from 70 degrees centrigrade to 80 degrees centrigrade. When a mixture of solid organic materials is used, it is preferable that the organic solids do not have substantially different melting points or the mixture is a soft solid at the chosen temperature. The material is then extruded. The extrusion temperature is preferably within 4°C of the heating temperature and more preferably, the extrusion is carried out at the same temperature as the temperature of the heating step. Extrusion can be carried out on a single or twin screw extruder or a die extruder with various configurations. It is particularly preferred to use a die extruder. The die roller design extruder which is especially suitable for the invention has two rollers rotating in the opposite directions, one is the knurling and the other is a die roller with perforations. The extruded, granulated material is typically in the form of noodles. The extruded material can be suitably cut as desired to get extrudates of uniform length. The cutter can be a part of the extruder or a separate cutter can be employed. The noodles are preferably of diameter 0.5 to 3 mm and length 0.1 to 6 mm. Preferably the noodles are of diameter 1.5 to 3 mm and 0.5 to 4 mm length. Preferably the noodles of uniform length that are so obtained are smoothened or provided with a suitable shape. Sharp edges and irregularities are suitably removed by using a merumiser. A typical merumiser consists of a vertical cylindrical vessel with a knurled plate at the bottom. The plate is mounted on a motor with a variable speed arrangement. The material to be smoothened is added after starting the revolution of the plate at the required rpm. It is preferred that the extruder material be provided a substantially spherical shape The material can be obtained in a substantially spherical shape by using a spherodiser. The spherodiser consists of a rotating disc with a chequered design plate. The rpm of the disc is suitably between 800 to 1200. The disc is maintained at a temperature of 58 to 78 degrees centigrade. Spherical granules of a suitable size can be obtained by selecting the plate pitch. Spherodisation can be carried out by placing the noodles obtained by extrusion in the bed of the spherodiser. The noodles are then spun and rolled till the noodles are converted into uniform spherical granules. The granules so obtained have a narrow shape and size distribution. The bulk density is also increased by using the process of the invention. The granule composition is chemically similar to the feed composition. The process of the invention is now suitably demonstrated by non-limiting examples. EXAMPLES: Extrusion of 12-hydroxy stearic acid: It is necessary to achieve a soft paste like consistency of the organic material, 12-hydroxy stearic acid (HSA) before extrusion in order to obtain desired granules. The melting point of HSA is 76 degrees centigrade. Table 1 shows that the material softens at a particular temperature range and extrusion is possible only in this temperature range. The material skin temperature is measured by using a thermocouple and refers to the temperature of the surface of the organic solid. Table 1: Material skin temperature(°C) Extrusion possible 50-56 Yes >56 No Table 1 shows that the temperature range of extrusion is critical. The process according to the invention is demonstrated in Example 1 and 2. Example 1: 2kg of 12- Hydroxy stearic acid (bulk density: 0.5 g/cc ) was taken in a tray. The tray was then heated to 60 degrees centigrade by means of hot air. The material skin temperature of 51.3 degrees centigrade was obtained in 65 minutes. The material was then fed to a die extruder. The extruder consisted of two rotors rotating in opposite directions, one of the rotors being solid and the other perforated. The perforation diameter was 2 mm. The rate of extrusion was 15kg/hr and the extruder was maintained at 58-60°C. The extruded material was then taken in a sherodiser which was heated to 58-60°C by use of hot air. The desired spherodisation occurred in 4 minutes. The sherodised material was next brought down to room temperature by natural convection. The 12-hydroxy stearic acid was obtained in a substantially spherical form. Bulk density after spherodising: 0.59 g/cc Example 2: 2kg of 12- Hydroxy stearic acid (bulk density: 0.5 g/cc ) was taken in a tray. The tray was then heated to 70 degrees centigrade by means of hot air. The material skin temperature of 54.6 degrees centigrade was obtained in 45 minutes. The material was then fed to a die extruder. The extruder consisted of two rotors rotating in opposite directions, one of the rotors being solid and the other perforated. The perforation diameter is 0.5 mm. The rate of extrusion was 15kg/hr and the extruder was maintained at 58-60°C. The extruded material was then taken in a sherodiser which was heated to 58-60°C by use of hot air. The desired spherodisation occurred in 4 minutes. The sherodised material was next brought down to room temperature by natural convection. The 12-hydroxy stearic acid was obtained in a substantially spherical form. Bulk density after spherodising: 0.61 g/cc. Thus, the process of the invention provides for granulated organic solids of a desired shape with advantageous properties. The process uses no or minimal binding and/or agglomeration aids. The granulated solid organic material is obtained in a desired shape, with a narrow particle size distribution and high bulk density. There is minimal dust present in the granulated material. Example 3: 2kg of hydrogenated castor oil (bulk density: 0.5 g/cc ) was taken in a tray. The tray was then heated to 95-100 degrees centigrade by means of hot air. The melting point of hydrogenated castor oil is 86°C. The material skin temperature of 80-81 degrees centigrade was obtained in 65 minutes. The material was then fed to a die extruder. The extruder consisted of two rotors rotating in opposite directions, one of the rotors being solid and the other perforated. The perforation diameter is 0.5 mm. The rate of extrusion was 15kg/hr and the extruder was maintained at 80-81 °C. The extruded material was then taken in a sherodiser which was heated to 80-81°C by use of hot air. The desired spherodisation occurred in 4 minutes. The sherodised material was next brought down to room temperature by natural convection. The hydrogenated castor oil was obtained in a substantially spherical form. Bulk density after spherodising: 0.61 g/cc. We claim: 1. A process for obtaining a solid organic material of desired shape and size comprising the steps of: i. heating the solid organic material to a temperature that is not higher than 4°C below the melting temperature of the organic material for at least 5 minutes ii. extruding the solid organic material at a temperature that is not higher than 4°C below the melting temperature of the organic material and optionally cutting the extrudate. 2. A process as claimed in claim 1 wherein the extrudate is preferably smoothened or provided a substantially spherical shape by merumerisation or spherodisation. 3. A process as claimed in claim 1 to 2 wherein the organic material is a castor oil and/or ricinoleic acid derivative. 4. A process as claimed in claim 3 wherein the castor oil derivatives are chosen from 12- hydroxy-stearic acid and hydrogenated castor oil. 5. A process as claimed in any of the preceding claims comprising the steps of: a) heating the castor and/or ricinoleic acid derivative or a mixture thereof to a temperature ranging from 45°C - 90°C. b) extruding the castor and/or ricinoleic acid or a mixture thereof at a temperature ranging from 45°C - 90°C. c) preferably smoothening or providing a substantially spherical shape to the extruded material by merumerisation or spherodisation. 6. A process as claimed in claim 5 wherein for the ricinoleic acid derivative is 12-hydroxy-stearic acid, the heating and extrusion temperatures are chosen between 50° and 56°C. 7. A process as claimed in claim 5 wherein for the hydrogenated castor oil, the heating and extrusion temperatures are chosen between 78° and 82°C. 8. A process as claimed in any of claims 1 to 7 wherein the extrusion can be carried out on a twin screw or single screw extruder or a die screw extruder. 9. A process as claimed in claim 8 wherein the extrusion is carried out on a die screw extruder with two rollers rotating in opposite directions, one the knurling and the other a die roller with perforations. 10. A process as claimed in any of claims 1 to 9 where the extruded material is in the form of noodles. 11.A process as claimed in claim 10, wherein the extruded noodles are merumerised or spherodised. Dated this 25th day of October 2002

Documents:

1055-mum-2001-abstract-(16-08-2004).doc

1055-mum-2001-abstract-(16-08-2004).pdf

1055-mum-2001-claims(granted)-(16-08-2004).doc

1055-mum-2001-claims(granted)-(16-08-2004).pdf

1055-mum-2001-correspondence(16-08-2004).pdf

1055-mum-2001-correspondence(ipo)-(16-11-2004).pdf

1055-mum-2001-form 1(31-10-2001).pdf

1055-mum-2001-form 19(23-06-2003).pdf

1055-mum-2001-form 2(granted)-(16-08-2004).doc

1055-mum-2001-form 2(granted)-(16-08-2004).pdf

1055-mum-2001-form 3(25-10-2002).pdf

1055-mum-2001-form 3(31-10-2001).pdf

1055-mum-2001-form 5(25-10-2002).pdf

1055-mum-2001-general power of attorney(29-01-2004).pdf