MXPA06010706A

MXPA06010706A - Biopolymer compositions and products thereof

Info

Publication number: MXPA06010706A
Application number: MXPA/A/2006/010706A
Authority: MX
Inventors: Nicolas Cade Dominique; Lucie Miralles Mariechristine; Anthony Scott Robert; Genevieve Odile Tardy Claire
Original assignee: Warnerlambert Company Llc
Priority date: 2004-03-22
Filing date: 2006-09-19
Publication date: 2007-04-20

Abstract

This invention relates to biopolymer-based compositions and biopolymer-based formed bodies such as film, sheet, capsule, casing or coating-film or spray thereof. In another embodiment, the invention relates to a process for producing a biopolymer-based starting material and biopolymer-based formed bodies such as cited above, for the manufacture of pharmaceutical, veterinary, food for cosmetic products.

Description

BIOPOLIMERIC COMPOSITIONS AND PRODUCTS OF THE SAME FIELD OF THE INVENTION This invention relates to compositions based on biopolymers and bodies formed based on biopolymers such as film, sheet, capsule, inner coating film or outer coating film or sprayer thereof. In another embodiment, the invention relates to a process for producing a starting material based on biopolymers and shaped bodies based on biopolymers as cited above, for the preparation of pharmaceutical, veterinary, food, cosmetics or other similar products, more particularly films for food wraps, aspic, or gelatins and preferably for predosed formulations such as hard or soft capsules, comprising a biopolymer or a mixture of biopolymers that are preferably selected from the group of polysaccharides originated by bacteria such as pullulan, soligel® or dextran, and / or polysaccharides originated by plants such as starch, starch derivatives, maltodextrin, or cellulose derivatives. BACKGROUND OF THE INVENTION One of the most preferred edible dosage forms for pharmaceuticals, dietary supplements and healthy food products are two-part capsules also referred to as hard capsules. The hard capsules are easy to swallow and insipid sheath. Some capsules can be opened and sprinkled over food or in water / juice if the consumer or patient has difficulty swallowing. Conventional hard capsules are made of gelatin by dip molding process. The immersion molding process is based on the ability to be fixed by cooling the hot gelatin solutions. For the industrial manufacture of pharmaceutical capsules, gelatin is more preferred for its gelling, film-forming and surfactant properties. The elaboration of hard gelatin capsules by means of the immersion molding process fully exploits their gelling and film-forming capabilities. A typical dip molding process comprises the steps of dipping mold clips into a hot gelatin solution, removing the clips from the gelatin solution, allowing the gelatin solution anchored onto the clips to be fixed by cold drying and dismantling the clips. so formed pods of the brooches. The fixation of the solution on the mold clips after immersion is the critical step to obtain a uniform thickness of the capsule sheath. This edible dosage form has several disadvantages. First, two-part capsules or hard capsules are used primarily for loading solid material such as powders, granules, pellets, tablets or combinations but rarely for loading liquids or suspensions of solids into liquids. Then, the range of application of this edible dosage form is reduced to oral administration. With regard to processing, the loading material is later loaded by the manufacturers of the formulation and not by the suppliers of capsules. Therefore, attempts have been made to develop an alternative administration system to the hard gelatin capsule. One of the most commercialized alternatives is the soft gelatin capsule or soft elastic gelatin. These capsules are typically loaded with a liquid containing the active ingredient. Due to its elastic, soft nature, some patients consider these capsules as easier to swallow than conventional tablets or hard gelatine capsules. Since the dosage form is generally swallowed, it is not necessary to aromatize or otherwise mask the often unpleasant taste of the pharmaceutical product. Soft gelatin capsules are also preferred for loading liquid in large quantities because they are easier to transport and avoid the need for the patient to measure a prescribed amount of liquid before dosing. US5916590 discloses a film-like composition in which a therapeutically effective amount of a pharmaceutical product is dissolved in a gelling agent such as gelatin to produce soft capsule used as a pharmaceutical dosage form. The gel can also be used to mold a two-piece hard gelatin capsule. The soft capsule can be seen as an appropriate alternative to hard capsules. Can be loaded with liquids, combination of miscible liquids and solid suspension in liquids. In addition, the application interval of this edible dosage form is large. In addition to oral administration, this dosage form can be used for pessans, suppositories and as a package in the cosmetics industry for products for breath fresheners, perfumes, bath oils and skin or tube-shaped cosmetics for hair care applications. single dose. Almost every soft capsule is manufactured using the rotary nozzle procedure patented by Scherer in 1933. Two independent procedures take place, often simultaneously, producing two different materials, the gel mass and the filler material. They both come together in the encapsulation procedure that produces wet soft capsules. The mass of the wet gel is made by mixing and melting together, under vacuum, the processing ingredients. In the encapsulation machine, the mass of molten gel flows through heated transfer tubes and is molded on chilled drums, forming two separate tapes. The thickness of the tapes is carefully controlled and checked periodically throughout the elaboration. The gel ribs traverse through rollers that provide proper alignment of the ribbons and apply lubricant to both surfaces of the ribbons. Each gel tape forms one half of the soft capsule. Finally, soft capsules are formed during the encapsulation step, using the two gel tapes and the filling material. The lubricated gel tapes are fed between a pair of nozzles that rotate in the opposite direction, the surface of which contains suitable size and shape compatible cavities that serve as molds to form the soft capsules. The nozzle cavities also seal both sides of the soft capsule and cut the soft capsule formed separating it from the residual gel tape. Located between the tapes and the rotating nozzles, the wedge fulfills three different functions during the encapsulation procedure. First, it heats the gel tapes near the dissolution temperature of the gel to ensure that the fusion of the two gel tapes takes place when the tapes are pressed together between the nozzles. Second, the wedge is part of the system that distributes the filling material from a positive displacement pump to each of the cavities. Finally, the wedge, in conjunction with the lubricant, provides a sealing surface against the belts to remove air and allows a seal to be formed between the sheaths and the filling material without the introduction of air into the product. Then the soft capsules are transported to a rotary drum dryer to initiate drying. Gelatin is a hydrocolloid that forms a colloidal solution in water, which presents a unique combination of useful properties. These properties include water solubility, solution viscosity, thermally reversible gelling properties and an ability to form very bright, strong, transparent and flexible films. In addition, the gels melt at body temperature and the films will dissolve when digested. Gelatin is a protein. Commercial uses of gelatin have been established in a wide range of industries, including applications in food, pharmaceutical, medical, photographic, cosmetic and technical products. Commercially, one of the main applications for gelatin is in the pharmaceutical industry, in the production of hard and soft capsules, where the ability of gelatin to form bright, transparent, flexible capsule walls is important. The ability of the gelatin capsules to dissolve in the stomach may also be necessary. Gelatin is also used for the microencapsulation of oils and vitamins (especially vitamins A and E) for edible and pharmaceutical uses. Despite the extraordinary properties shown by gelatin, alternatives to gelatin are currently being sought, particularly in the pharmaceutical industry. Recently, a global consumer demand for capsules of non-animal natural origin increases requiring the replacement of gelatin, a compound of animal origin. Successful industrial examples are capsules made with modified cellulose such as hydroxypropylmethylcellulose (HPMC). Other alternatives to gelatin are exopolysaccharides selected from the pullulan, dextran or soligel® group and are well known for their gelling and elastic properties. Pullulan is a natural water-soluble polysaccharide produced by Pullularia pullulans and consists of repeating units of maltrose linked by D-1 bonds, 6 for which Hayashibara Inc. had developed mass production capacity in 1973. Pullulan is used for multiple application including food, pharmaceutical products, cosmetic products, mainly due to its characteristics of membrane formation, adhesion, biodegradable capacity and edibility. It is also easy to process into films, sheets, and molded goods and has been referred to as an edible plastic. Hard pullulan capsules are easy to swallow, quickly soluble and can effectively mask taste and odor. Pullulan is pseudo-thermoplastic and can thus be compression molded or extruded at elevated temperature. JP5065222 discloses a soft capsule, capable of stabilizing an easily oxidizable substance enclosed therein, exhibiting easy solubility and being able to withstand a production process by drilling. The soft capsule is obtained by mixing a capsule film substrate such as gelatin, agar or carrageenan with pullulan. Document US3784390 corresponding to documents FR2147112 and GB1374199 discloses that certain mixtures of pullulan with at least one member of the group consisting of amylose, polyvinyl alcohol and / or gelatin can be modeled by compression molding or extrusion at elevated temperatures. or by evaporating water from its aqueous solutions to form molded bodies, such as films or external coatings. To retain the valuable properties of pullulan to an important degree the mixture should not contain more than 120 percent amylase, 100 percent alcohol poly (vinyl alcohol) and / or 150 percent gelatin based on the weight of pullulan in the mixture. The exopolysaccharides marketed under the trade name Soligel® involve six neutral sugars, one uronic acid in the main chain and one pyruvyl substituent per repeated unit as well as acetyl substituents but not exactly located by Villain-Simonet et al. in International Journal of Biological Macromolecules 27 (2000) 65-75. The exopolysaccharide is produced by a soil bacterium Rhizobium leguminasorum and is applicable in the cosmetics, food, pharmaceutical and petroleum industries and can form, as indicated in WO9835993, a transparent and elastic gel. Dextran is a high molecular weight polysaccharide synthesized by microorganisms (specifically: Leuconostoc mesenteroides and Leuconostoc dextranicum) and consists of D glucose linked by 1,6 bonds (and a few 1,3 and 1,4 bonds). In EP0888778, a capsule formulation comprising gelatin and a polysaccharide such as dextran was prepared by shaping the drug delivery composition in a capsule and loading a biologically active substance into the capsule which may be hard or soft and prepared using a snap mold or rotary nozzle procedures. The capsules described are intended for use as a selective colon drug delivery system. Although capsules comprising pullulan, dextran and soligel® were mentioned in several patents or applications, there remains a need for a capsule that does not contain ingredients derived from animals. The new capsule ingredients should be able to form mechanically strong products, transparent, as an alternative to or substitute for gelatin, in particular for edible and ingestible pharmaceutical applications.

Other alternatives to animal-based systems are film-forming compositions of plant origin, such as starch or cellulose. Cellulose is the main constituent of all plant tissues and fibers. It is a carbohydrate, (CßHioOsJn, isomer of starch, and is convertible into starches and sugars by the action of heat and acids. WO01 / 66082 relates to a gel composition using combination of starch and carrageenan iota by its property of Maltodextrin is a partially hydrolyzed starch product The present invention overcomes this problem by using water soluble, high molecular weight biopolymer, which is surprisingly capable of producing clear aqueous solutions and products of suitable mechanical strength, and is therefore suitable for use in known processes for the preparation of hard and soft capsules The problem to be solved is therefore the provision of an edible film-forming composition containing a biopolymer or a mixture of biopolymers, selected from the group of pullulan, soligel® , dextran, maltodextrin, starch derivatives and cellulose derivatives in substitution of animal gelling components.

SUMMARY OF THE INVENTION This invention relates to compositions containing a biopolymer or a mixture of biopolymers, selected from polysaccharide originated by bacteria or polysaccharide originated by plants. More particularly, the invention relates to a film forming composition. The films formed can have variable hardness properties that allow non-limited molding technique, from soft formed bodies to hard formed bodies with a desired thickness. Surprisingly, the inventors have found that the composition comprising: at least one biopolymer, at least one plasticizer and water has an effective film-forming property, which allows the preparation of starting material and / or bodies formed. Additionally, the composition based on biopolymers may also comprise at least one active ingredient which may be a pharmaceutically active ingredient and the like but is not limited thereto. In another embodiment, the present invention relates to a process for the preparation of formed bodies, manufactured from the composition of the present invention characterized by the steps of: a) processing a mixture containing at least one biopolymer, at least one plasticizer, and water heating and kneading while, giving a mass capable of being processed thermoplastically in a processing device; b) preparation of at least one starting material and c) reshaping the starting material to give a body formed in a continuous and intermittent molding process. The formed bodies can be films, sheets, capsules, internal coating film or outer coating film or sprayer. The capsules can be hard or soft capsules. Those capsules can be loaded with an active ingredient in solid or liquid form. The hard capsule is obtained by a well-known method of immersion molding and soft capsules by conventional rotary nozzle method, procedures briefly described above. The starting material can have variable shapes (ball, film, flat and / or square shapes). DETAILED DESCRIPTION OF THE INVENTION This invention relates to compositions based on biopolymers that contain a biopolymer or a mixture of biopolymers. More particularly, the invention relates to a film-forming composition. The formed film can have variable hardness properties that allow non-limited molding technique, from soft formed bodies to hard formed bodies with a desired thickness. The composition of the invention is more preferably edible or acceptable as a food, is used for food wrapping or is in contact with food. The composition of the invention is more preferably a pharmaceutically acceptable composition. The composition is used for the manufacture of pharmaceutical, veterinary, food, cosmetic or other similar products.

The products made from the composition of the invention are shaped bodies made by the process as described below or using any means and procedures already known to the skilled person. Those formed bodies may be films, sheets, capsules (soft or hard capsule), internal coating films, outer coating films or sprayers or predosed formulations and more preferably may be in the form of a film. The examples given in this document are not limited. A second embodiment, the present invention relates to a process for producing a starting material and formed bodies. Surprisingly, the inventors have found that the composition comprising: at least one biopolymer, at least one plasticizer and water has an effective film-forming property, which allows the preparation of starting material and / or bodies formed which will be detailed below. "Effective film-forming property" is defined as the ability of the composition to remain in a solid form at a specific temperature and preferably at room temperature. Another important property is the ability to disintegrate the film at a specific temperature and preferably at body temperature. The composition of the invention is highly processable. As indicated above, the invention provides a composition for the preparation of shaped bodies used as an enteric or colonizing delivery system. The amount of the components of the composition will be adjusted in order to obtain specific release, enteric or colonic location. The composition based on biopolymers does not require the use of auxiliary gelling agents and gelling systems such as carrageenans, gellan and pectin and their associated metal ions as promoters of the gel structure. A positive consequence of the absence of the aforementioned gelling agents is that the dissolution of the formed bodies (capsules for example) made from the composition is not affected by the presence of ions either in the dissolution media when the rehearses in vito or in the stomach or intestinal tract when absorbed. It is well documented that when the dissolution medium contains sufficient potassium gel-forming ions, the dissociation of the aggregates is delayed. As a consequence the gel structure of gellan and carrageenan remains, leading to reduced solubility. When the in vitro buffer medium contains sodium cations, the gel breakdown is faster. A great advantage of the shaped bodies of the composition of the invention such as a film on gelatin films for example is the faster preparation time, which results from the use of the extrusion process against conventional melting processes. With the extrusion process, the film is formed in a few minutes compared to the several hours necessary to melt and remove bubbles from a gelatin solution prior to film casting. Preferably, the biopolymer is polysaccharide originated by bacteria or polysaccharide originated by plants. The polysaccharide originated by preferred bacteria is an external polysaccharide, namely exopolysaccharide. Suitable exopolysaccharides include, but are not limited to pullulan, soligel® and dextran. The polysaccharides originated by preferred plants include, but are not limited to maltodextrin, starch and starch derivatives and cellulose derivatives. According to the present invention, the biopolymers or mixture of biopolymers are selected from the group of pullulan, soligel®, dextran, maltodextrin, starch derivatives and cellulose derivatives. The biopolymer can be used in an amount of 30 to 80% of the total weight of the composition. In a preferred embodiment the biopolymer is used in an amount of 40 to 70% of the total weight of the composition. In a more preferred embodiment the biopolymer is used in an amount of 50 to 60% of the total weight of the composition. In accordance with the present invention, the plasticizers or the mixture of plasticizers are used to make the composition of the invention more elastic and flexible and are selected from the group consisting of organic acids of polyalcohols, hydroxy acids, amines, acid amides, sulfoxides and pyrrolidones. In a preferred embodiment of the present invention the organic acids of polyalcohols (or polyhydric alcohols) are selected from the group of sorbitol, mannitol glycerol, xylitol, maltitol, maltisorb, propylene glycol, lactitol, trehalose, sorbitan esters and sorbitol anhydride and mixtures thereof. the same.The plasticizer or a mixture of plasticizers can be added in an amount of 0% to 80% or 0% to 40% of the total weight of the composition. In a preferred embodiment, the plasticizer or mixture of plasticizers are added in an amount of 5% to 35% or 10% to 30% of the total weight of the composition and in a more preferred embodiment of 15% to 25% of the total weight of the composition. The amount and choice of the plasticizer helps to determine the hardness of the final product or in the current case of the formed body and can affect the dissolution or disintegration of the composition of the invention, as well as its physical and chemical stability. Water is critical to ensure proper processing during gel preparation. The composition of the present invention contains at least 5% water of the total weight of the composition, in a preferred embodiment of 10% to 40% of the total weight of the composition and in a most preferred embodiment of 10% a 25% of the total weight of the composition. The composition of the invention as described above may additionally contain an opacifier or a mixture of opacifiers. The opacifier was added to the composition of the invention in order to obtain an opaque gel suspension or a final product to protect the charged active ingredients or light sensitive contents. The opacifiers may be present in an amount of 0.1% to 4% of the total weight of the composition and are selected from the group of titanium dioxide, calcium carbonate, iron oxide and glycol stearate. A preferred embodiment of the present invention is titanium dioxide. The composition as described above may additionally contain a pharmaceutically acceptable coloring agent or acceptable coloring agent as a food or a mixture of coloring agents in the range of 0% to 10% of the total weight of the composition of the invention. The coloring agent can be selected from azo, quinophthalone, triphenylmethane, xanthene or indigo stains or natural stains or mixtures thereof. The coloring agents can also be selected from the group of patent blue V, bright green acid BS, red 2G, azorubine, ponceau 4R, amaranth, red 33 D + C, red 22 D + C, red 26 D + C, red 28 D + C, yellow 10 D + C, yellow 2 G, yellow 5 FD + C, yellow 6 FD + C, red 3 FD + C, red 40 FD + C, blue 1 FD + C, blue 2 FD + C, green 3 FD + C, bright black BN, carbon black, black iron oxide, red iron oxide, yellow iron oxide, riboflavin, carotenes, anthocyanins, turmeric, cochineal extract, chlorophyll, canthaxanthin, caramel and betanin or mixture of same. The composition is clear and colorless as the obtained material formed by evaporation of water from a solution of exopolysaccharides and has a high gloss. The bodies formed of exopolysaccharides are flexible and have resistance to folding. The mechanical and optical properties of the material are not altered by the passage of time and storage at very high or very low relative humidity. It does not become brittle at temperatures as low as -10 ° C. It does not retain static electricity charges and does not easily support the growth of microorganisms. Even bodies formed of very fine exopolysaccharides are almost impervious to atmospheric oxygen. It has also been reported that the composition is homogeneous and does not present any unmelted material or particle. In another embodiment, the present invention relates to a process for the preparation of formed bodies, starting from the composition of the present invention characterized by the steps of: d) processing a mixture containing at least one biopolymer, at least one plasticizer, and water heating and kneading while, giving a mass capable of being processed thermoplastically in a processing device; e) preparation of at least one starting material and f) remoulding the starting material into a body formed in a continuous or intermittent molding process. The formed bodies can be films, sheets, capsules, bodies that form internal lining or bodies that form external coating. The capsules can be hard or soft capsules. Those capsules can be loaded with an active ingredient in a solid or liquid form. The hard capsule is obtained by a well-known dip-molding process and the soft capsules by a conventional rotary nozzle method. The procedures are briefly described above. The process consists in mixing at least one biopolymer and at least one plasticizer in water, giving a thermoplastically processable mass in a processing device. The processing temperature will not exceed 160 ° C, in a preferred embodiment it will not exceed 140 ° C and in a more preferred embodiment it will not exceed 100 to 110 ° C. The processing device has a rotation speed between 150 and 300 rpm. The processing pressure is in a range of 2000000 to 7000000 pass (from 20 to 70 bar). The thermoplastically processable composition is referred to in the present invention as starting material. A desired shape is given to the thermoplastically processable mass using suitable means and procedures already known to the skilled person. The starting material may have variable shapes (ball, film, flat, strip and / or square shapes). The present invention will be exemplified by using an extruder and preferably a twin-screw extruder as the medium. In this preferred embodiment the starting material is in a strip film form. The size and shape of the starting material should be chosen appropriately for the next step in the procedure that is the regrind. In this stage of the process the starting material is at such a temperature and flexible in such a way that the starting material can be given the desired shape. The starting material obtained by the present process is at least one extruded strip film having a thickness of 40 μm to 1000 μm. In a preferred embodiment, the extruded strip film has a thickness of 250 μm to 850 μm or 400 μm to 750 μm and in a more preferred embodiment, the extruded strip film has a thickness of 600 μm to 700 μm. Preferably the starting material is in a strip film form. The reduced amount of water in the films obtained compared to the water content of more than 40% with another alternative dissolution composition with modified cellulose derivatives or starches results from the composition of the invention and its processing with the extruders. An obvious benefit of this lower water content of the obtained starting material or preferably a film, is a significantly shorter drying time for the finished products. The residual moisture of the extruded starting material is between 10% and 30% of the total weight of the extruded starting material. Preferably, the residual moisture of the extruded starting material is between 10% and 25% of the total weight of the extruded starting material. Finally, the starting material is cast in a body formed in a continuous or intermittent molding process. In a preferred embodiment, the two extruded strip film stock materials are rolled into a formed body. The remoulding can be done by molding (i.e. molded by immersion of capsules), rotating nozzle (i.e. molding of soft capsules) or by any means and procedure already known to the skilled person. The means and procedure for the remodeling are defined taking into account the form that is desired and taking into account the use of it. In a preferred embodiment, the formed body is selected from the list of film, sheet, capsule, inner liner and outer coating. In a more preferred embodiment the capsule is a hard capsule or a soft capsule. In another embodiment more preferred the formed body is a film of such size that the film can be placed in the oral cavity. The formed body can be used as a container for the unit dosage form or delivery system. Packaging for unit dosage form and administration system should be understood as any products of the composition as described in the present invention and containing an active ingredient or substance. Those ingredients or active substances can be food, food additives, pharmaceuticals, chemicals, cosmetics and dyeing but also spices, fertilizer combinations, seeds, paint, construction products and agricultural products. The active ingredients or substances can be added to the processing mixture of the composition of the invention or can be charged later (in the reforming stage for example) into the formed body in a solid or liquid form. In case of soft capsule, the loading takes place simultaneously to the forming process. The extruded starting material of process step b) has an elongation at break at room temperature between 100% and 1000%, in a preferred embodiment between 200% and 500% and in a most preferred embodiment between 200 and 500%. % and 300%. The elongation at break is considered before the drying step. The Young's modulus of the extruded starting material is at ambient conditions in the range of 0.5 to 40 MPa, in a preferred embodiment it is 1 to 10 MPa and in a most preferred embodiment it is 2 to 4 MPa. Young's modulus is considered before the drying step. The extruded starting material in the form of a flat film is preferably molded using the rotary nozzle technology wherein the wedge temperature is between 50 and 100 ° C, preferably 60 to 90 ° C, and more preferably 70 to 50 ° C. 85 ° C. The processing mixture comprising biopolymer (s), plasticizer (s), and water is as described above. The processing mixture as described in step a) may additionally contain an opacifier as described above. The processing mixture as described in step a) may additionally contain pharmaceutically or food-acceptable coloring agents as described above. In a preferred embodiment relating to capsule, lubricants for release of the mold are used to facilitate removal of the mold clips from the capsule forming core. By "lubricant" is meant a material capable of reducing friction between the mold clasps and the inner surface of the formed capsule. The lubricant is compatible with the capsule (ie, should not degrade the capsule), facilitates the removal of the capsule from the mold snaps and is pharmaceutically acceptable (ie, non-toxic). Although the lubricant may be a single lubricant compound, it may also be a "lubricant composition" having one or more lubricating compounds and, optionally, other additives or diluents present therein. Many suitable lubricants are available and used in capsule manufacturing. Examples of possible lubricants include: silicone oil; sodium or magnesium lauryl sulfate; fatty acids (for example, stearic acid and lauric acid); stearates (for example, magnesium stearate, aluminum stearate, or calcium stearate); boric acid; vegetable oils; mineral oils (for example paraffin); phospholipids (for example lecithin); polyethylene glycols; sodium benzoate and mixtures of the above, sodium stearyl fumarate, hydrogenated vegetable oil, hydrogenated castor oil, hydrogenated cottonseed oil, stearic acid and calcium stearate, and the like. Often, other components are present in the lubricant. For example, calcium soap can be dispersed in the oil lubricant. Sometimes, the lubricant dissolves in oil, for example. Such lubricant compositions are well known in the art and are intended to be encompassed by the term "lubricant". The liberator, lubricant or mold release agent is used in an amount of 0.25 to 1% of the processing mixture. Finally the shaped bodies are dried with any known means and procedures. In the case of soft capsules this step can be done with air at 30 ° C in 1 hour. After drying the thickness of the material that forms the formed bodies decreases. The thickness is in a range of 250 μm to 500 μm and preferably 300 μm to 400 μm. As indicated above, the formed body is formed as films, sheets, capsules, internal coating film or outer coating film or sprayer which can be used as a package for unit dosage form or administration system. In a preferred embodiment the formed body can be an external coating of tablets, pellets or capsules. In a more preferred embodiment the outer coating is an enteric outer coating or an external colonic coating. The present invention will now be described with reference to the accompanying examples. These examples are intended to illustrate the invention and the scope of the invention should not be considered limited to the embodiment described herein.

CAS0 1: Examples of film-forming compositions with their conditions and extrusion properties-Example 1: Pullulan polymer 61.7% Excipients and processing aids Sorbitol 23% Water 15.3% Processibility +++ Extrusion temperature in ° C 105 Extrusion pressure in passages (bars) 3200000 (32) Film-forming properties +++ Adhesion to the processing surfaces None% elongation 360% Young's module 1 MPa Example 2: Pullulan polymer 61.6% Excipients and processing aids Sorbitol 15.4% Mannitol 3.8% Water 19.2% Processibility +++ Extrusion temperature in ° C 105 Extrusion pressure in passéals (bars) 3800000 (38) Film forming properties +++ Adhesion to processing surfaces None % Elongation 320% Young's Module 2 MPa Example 3: Pullulan Polymer 66.6% Excipients and processing aids Sorbitol 15.1% Mannitol 3.8% Water 14.5% Processibility +++ Extrusion temperature in ° C 105 Extrusion pressure in passéals (bars) 3500000 (35) Film-forming properties +++ Adhesion to processing surfaces None% elongation 260% Young's modulus 4 MPa Example 4: Pullulan Polymer 61% Excipients and processing aids Sorbitol 17.6% Mannitol 4.4% Water 17% Processibility +++ Extrusion temperature in ° C 105 Extrusion pressure in passéals (bars) 3000000 (30) Film-forming properties +++ Adhesion to processing surfaces None% elongation 300% Young's modulus 3.7 MPa Example 5: Pullulan polymer 48.4% Maltodextrin 12.1% Excipients and processing aids Sorbitol 15.8% Mannitol 4.0% Water 19.7% Processibility +++ Extrusion temperature in ° C 95 Extrusion pressure in passages (bars) 2600000 (26) Film-forming properties +++ Adhesion to the processing surfaces None% elongation 315% Young's Module 3,2 MPa Example 6: Pullulan 60% Soligel 3.2% Polymer Excipients and processing aids Sorbitol 14.7% Mannitol 3.7% Water 18.4% Processibility +++ Extrusion temperature in ° C 105 Extrusion pressure in passéals (bars) 5600000 (56) Film forming properties +++ Adhesion to processing surfaces None Elongation% 240% Young's Module 2.5 MPa Example 7: 64.5% Dextran Polymer Excipients and processing aids Sorbitol 14.2% Mannitol 3.6% Water 17.8% Processibility + Extrusion temperature in ° C 90 Extrusion pressure in passages (bars) 3200000 (32) Film-forming properties +++ Adhesion to processing surfaces None elongation% 250% Young's module 2.2 MPa For all examples: Pullulan from Hayashibara Japan, Soligel® from ARD France, Maltodextrin Glucidex 19 from Roquette France Dextran 70 from Amersham Bioscience Amersham foot Buckinghamshire Kingdom United Sorbitol of Neosorb 70/70 from Roquette France Mannitol from Roquette France Processability: (from excellent +++ to poor -) describes the behavior of the powder in the supply of the powder to the extruder, the general behavior during the extrusion process; Classification of higher to lower properties of film formation is based on observation of the obtained film (from excellent +++ to poor -).

Elongation% and Young's modulus are measured on the film immediately after extrusion (there is no drying step).

CASE 2: Examples of capsules made from film forming compositions with their processing conditions and properties. The capsules were made under the following conditions: The dry components (powder) of the film composition are supplied in the extruder under a controlled weight feed (Provider of Weight Loss of Brabender Technologie KG, Duisburg Ge); the liquid part of the film composition is added to the extruder with a peristaltic dosing pump (from Watson-Marlow Bredel Inc. Wilmington, MA, USA) with precise flow control. The extruder used is a twin-screw extruder (from Thermo PRISM, Stone, Staffordshire, England) equipped at its outlet with an extrusion die for stripping film stock with adjustable slot thickness. The extruded starting material is "entrained" from the extruder by means of a conveyor belt (from Linatec Feyzin Rhone, France) with adjustable speed. The starting material is then passed over the greasing modules of the machine making the soft capsules (from Technophar Windsor, Ontario, Canada), supplied on the nozzle rollers. As for conventional soft elastic capsules, the two starting materials in strip film form were processed under the wedge block at the appropriate temperature for preheating and preconditioning of the composition to allow sealing. The capsule was loaded and formed following the procedure of making conventional gelatin soft capsules. The formed capsules were removed from the network and transferred into the rotary drum dryer with air at 30 ° C for one hour. The additional drying was carried out in trays. The thickness of the films was measured directly after the formation of capsules without drying. Example 1: Pullulan Polymer 61.7% Excipients and processing aids Sorbitol 23% Water 15.3% Charged product Paraffin oil (fluid) from Cooper Melun France Wedge temperature in ° C 70-75 Charge pressure in pascals (bars) ) 400000 (4) Film thickness before drying 750 μm Capsule opening time 2 minutes 30 seconds Dry film thickness 400 μm Example 2: Pullulan polymer 66.6% Excipients and processing aids Sorbitol 15.1% Mannitol 3, 8% Water 14.5% Product loaded Paraffin oil (fluid) Cooper Melun France Wedge temperature in ° C 60-70 Loading pressure in pascals (bars) 400000 (4) Thickness of film before drying 700 μm Time of Capsule opening 2 minutes Dry film thickness 350 μm Example 3: Pullulan polymer 66.6% Excipients and processing aids Sorbitol 15.1% Mannitol 3.8% Water 14.5% Product loaded Vitamin E 1000 IU of ADM Archer Daniels Midland Company Decatur, IL, USA Wedge temperature in ° C 90 Load pressure in pascals (bars) 400000 (4) Film thickness before drying 700 μm Capsule opening time 1 minute 30 seconds Dry film thickness 350 μm Example 4: Pullulan 61% polymer Excipients and processing aids Sorbitol 17.6% Mannitol 4.4% Water 17% Charged product Evening primrose oil (Mini 9% GLA) from Henry Lamotte GmbH Bremen Germany Wedge temperature in ° C 85-90 Loading pressure in Pascals (bars ) 400000 (4) Film thickness before drying 650 μm Capsule opening time 1 minute 30 seconds Dry film thickness 320 μm Example 5: Pullulan polymer 48.4% Maltodextrin 12.1% Excipients and processing aids Sorbitol 15, 8% Mannitol 4.0% Water 19.7% Product loaded Paraffin oil (fluid) from Cooper Melun France Wedge temperature in ° C 65 Load pressure in pascals (bars). 400000 (4) Film thickness before drying 680 μm Capsule opening time 1 minute Dry film thickness 350 μm

Claims

1. Film forming composition comprising at least one biopolymer, at least one plasticizer and water.

2. Composition according to claim 1 in which the biopolymer or a mixture of biopolymers are polysaccharide originated in bacteria.

3. Composition according to claim 2, wherein the polysaccharide originated in bacteria is an exopolysaccharide and is selected from the group of pullulan, soligel® and dextran.

4. Composition according to claim 1 in which the biopolymer or a mixture of biopolymers are polysaccharide originated in plants.

5. Composition according to claim 4, wherein the polysaccharide originated in plants is selected from the group of maltodextrin, starch derivatives or cellulose derivatives.

6. Composition of claims 1 to 5 wherein the composition is preferably a pharmaceutically acceptable or acceptable food composition and preferably in the form of a strip film.

7. Composition according to claim 1 wherein biopolymer is used in an amount of 30 to 80% of the total weight of the composition, in a preferred amount of 40 to 70% of the total weight of the composition or in a more preferred amount of the composition. 50 to 60% of the total weight of the composition.

8. Composition according to claim 1 wherein the plasticizer or mixture of plasticizers are selected from the group of organic acids of polyalcohols, hydroxy acids, amines, acid amines, sulfoxide and pyrrolidones.

9. Composition according to claim 8 in which organic acids of polyalcohols are selected from the group of sorbitol, mannitol glycerol, xylitol, maltitol, maltisorb, propylene glycol, lactitol, trehalose, sorbitan esters and sorbitol anhydride or mixtures of.

10. Composition according to claims 8 and 9 wherein the plasticizer is in an amount of 0 to 40% of the total weight of the composition, in a preferred amount of 5 to 35% of the total weight of the composition, in a quantity especially preferred from 10 to 30% of the total weight of the composition or in a more preferred amount of 15 to 25% of the total weight of the composition.

11. Composition according to claim 1 wherein the water is in an amount of at least 5% of the total weight of the composition, in a preferred amount of 10 to 40% and in a more preferred amount of 10 to 25% of the total weight of the composition.

12. Composition according to claim 1, wherein the composition contains at least one opacifier.

13. Composition according to claim 12, wherein the opacifier is selected from the group of titanium dioxide, calcium carbonate, iron oxide or glycol stearate.

14. Composition according to claims 12 and 13 wherein the opacifier is preferably titanium dioxide.

15. Composition according to claims 12 to 14, wherein the opacifier or the mixture of opacifiers are in the range of 0.1% to 4% of the total weight of the composition.

16. Composition according to claim 1, wherein the composition contains at least one coloring agent.

17. Composition according to claim 16, wherein the coloring agent is selected from dyes of the group azo-, quinophthalone-, triphenylmethane-, xanthene- or indigo, and natural dyes or mixtures thereof and is selected from patent blue V, bright green acid BS, red 2G, azorubine, ponceau 4R, amaranth, red 33 D + C, red 22 D + C, red 26 D + C, red 28 D + C, yellow 10 D + C, yellow 2 G, yellow 5 FD + C, yellow 6 FD + C, red 3 FD + C, red 40 FD + C, blue 1 FD + C, blue 2 FD + C, green 3 FD + C, black glossy BN, carbon black, black oxide iron, red iron oxide, yellow iron oxide, riboflavin, carotenes, anthocyanins, turmeric, cochineal extract, chlorophyll, canthaxanthin, caramel or betanin.

18. Composition according to claims 16 and 17, wherein the coloring agent or the mixture of coloring agents are in the range of 0% to 10% of the total weight of the composition.

19. Use of the composition according to any preceding claims for preparation of starting material and / or formed body.

20. Use according to claim 19 wherein said starting material is preferably in the form of a strip film.

21. Use according to claim 19 wherein said formed body is film, capsule, sheet, inner coating film or outer coating film or spray.

22. Use according to claim 19 wherein said formed body is a package for unit dosage form or a delivery system.

23. Body formed of composition according to claims 1 to 18.

24. Shaped body and / or composition starting material according to claims 1 to 18 containing food products, food additives, pharmaceuticals, chemicals, staining products, spices, fertilizer combinations, seeds, cosmetics, paints, construction products and agricultural products.

25. Body formed according to claims 23 and 24 wherein said formed body is selected from the list of film, sheet, capsule, inner coating film or outer coating film or spray.

26. Capsule according to claim 25 wherein said capsule is a hard or soft capsule.

27. Use of body formed according to claims 23 to 26 as a package for unit dosage form or administration or enteric system or as a container for colonic administration system.

28. Process for producing formed bodies of composition according to claims 1 to 18 characterized by the steps of: a) processing a mixture containing at least one biopolymer, water at least one plasticizer, and heating and kneading while, giving a processable mass thermoplastically in a processing device; b) preparation of at least one starting material, and c) remoulding the starting material into a body formed in a continuous or intermittent molding process.

29. Process according to claim 28 in which the biopolymer or a mixture of biopolymers are as defined in claims 2 to 5.

30. Process according to claim 28 in which biopolymer is used in an amount of 30 to 80% of the total weight of the processing mixture, in a preferred amount of 40 to 70% of the total weight of the processing mixture or in a especially preferred amount of 50 to 60% of the total weight of the processing mixture.

31. Process according to claim 28 in which the plasticizer or the mixture of plasticizers are selected from the group of organic acids of polyalcohols, hydroxyl acids, amines, acid amines, sulfoxides and pyrrolidones.

32. Process according to claim 31 wherein organic acids of polyalcohols are selected from the group of sorbitol, mannitol, glycerol, xylitol, maltitol, maltisorb, propylene glycol, lactitol, trehalose, sorbitan esters and sorbital anhydride.

33. Process according to claim 31 wherein the plasticizer is in an amount of 0 to 40% of the total weight of the processing mixture, in a preferred amount of 5 to 35% of the total weight of the processing mixture, in a especially preferred amount of 10 to 30% of the total weight of the processing mixture or in a more preferred amount of 15 to 25% of the total weight of the processing mixture.

34. Process according to claim 28, wherein the processing mixture a) contains at least 5% water, preferably 10 to 40%, more preferred 10 to 25% of the total weight of the processing mixture.

35. Process according to claim 28 in which the composition contains at least one opacifier.

36. Process according to claim 35, wherein the opacifier is selected from the group of titanium dioxide, iron oxide or glycol stearate.

37. Process according to claims 35 to 36, wherein the opacifier is preferably titanium dioxide.

38. Process according to claim 35, wherein the opacifier or mixture of opacifiers are in the range of 0.2% to 0.5% of the total weight of the processing mixture.

39. Process according to claim 28, wherein the composition contains at least one coloring agent.

40. Process according to claim 39, wherein the coloring agent is selected from the group of azo-, quinophthalone, triphenylmethane-, xanthene or indigoid stains, iron oxides or hydroxides, titanium dioxide or natural stains or mixtures thereof and also from the following non-limited list: patent blue V, bright green acid BS, red 2G, azorubine, ponceau 4R, amaranth, red 33 D + C, red 22 D + C, red 26 D + C, red 28 D + C , yellow 10 D + C, yellow 2 G, yellow 5 FD + C, yellow 6 FD + C, red 3 FD + C, red 40 FD + C, blue 1 FD + C, blue 2 FD + C, green 3 FD + C, bright black BN, carbon black, black iron oxide, red iron oxide, yellow iron oxide, titanium dioxide, riboflavin, carotenes, anthocyanins, turmeric, cochineal extract, chlorophyll, canthaxanthin, caramel or betanin.

41. Process according to claims 39 and 40, wherein the coloring agent or mixture of coloring agents are in a range of 0% to 10% of the total weight of the processing mixture.

42. Process according to claim 28, wherein the mixture applied in a) contains lubricant or mold release agent.

43. Process according to claim 42, wherein the lubricating or demolding agent is selected from silicone oil; sodium or magnesium lauryl sulfate; fatty acid stearates; boric acid; vegetable oils; mineral oils; phospholipids; polyethylene glycols; sodium benzoate; and mixtures of the above, sodium stearyl fumarate.

44. Process according to claims 42 and 43, wherein the releasing, lubricating or releasing agent is used in an amount of 0.25% to 1% of the processing mixture.

45. Process according to claim 28 in which the starting material is an extruded material.

46. Process according to claim 28, wherein the processing device is an extruder and more preferably a twin-screw extruder.

47. Process according to claim 28, wherein the processing temperature does not exceed 160 ° C, the preferred processing temperature is 140 ° C and the especially preferred processing temperature range is 100 to 110 ° C.

48. Process according to claim 28, wherein the processing speed is between 150 and 300 rpm.

49. Process according to claim 28, wherein the processing pressure is between 4000000 and 7000000 pascals (40 to 70 bars).

50. Process according to claim 28, wherein the thickness of starting material in b) is from 40 μm to 1000 μm, from 250 μm to 850 μm and from 600 μm to 700 μm is especially preferred.

51. Process according to claim 28 for the preparation of starting material and / or formed body.

52. Process according to claim 51 wherein said starting material is in a strip film form.

53. Process according to claim 28 wherein said formed body is selected from the group of film, capsule, sheet, inner coating film or outer coating film or spray.

54. Process according to claim 53 wherein said capsule is a hard or soft capsule.

55. Process according to claim 28 wherein the formed body is a package for unit dosage form, an administration system or an enteric or colonic administration system.

56. Process according to claims 28, 51 to 55 wherein the formed body and / or composition starting material according to claims 1 to 15 contain food products, food additives, pharmaceuticals, chemicals, staining products, spices, fertilizer combinations, seeds, cosmetics, paints, construction products and agricultural products.

57. Process according to claim 28, wherein the residual moisture of the film extruded in b) is comprised between 10 and 30%, preferably 10 to 25%.

58. Process according to claim 28, wherein the elongation at break of the extruded film in b), under ambient conditions, is comprised between 100 and 1000%, preferably 200 to 500%, more preferred 200 to 300 %.

59. Process according to claim 28, wherein the Young's modulus of the film extruded in b), at ambient conditions, is between 0.5 and 40 MPa, preferably 1 to 10 MPa, more preferred 2 to 4 MPa .

60. Process according to claim 28, wherein the forming process in c) is preferably the rotary nozzle technology.

61. Process according to claim 28, wherein the temperature of the wedge is between 50 and 100 ° C, preferably 60 to 90 ° C, more preferred 70 to 85 ° C.