Homogeneous, thermoreversible gel film containing kappa-2 carrageenan and soft capsules made therefrom

[0001] This application uses priority based on US Provisional Application No. 60/462785 filed April 14, 2003.

TECHNICAL FIELD OF THE INVENTION [0002] The present invention relates to a homogeneous, thermoreversible gel film comprising a film-forming amount of kappa-2-carrageenan and optionally at least one agent of the following: a plasticizer, a second film former, a filler, a pH adjusting agent; and methods of making it. The present invention furthermore relates to soft capsules and solid forms containing a gel foil, as well as methods for their preparation.

BACKGROUND OF THE INVENTION [0003] For a long time, gelatin has been used to prepare films used in the production of soft capsules. It is a collagen protein hydrolyzate, usually produced by boiling bones and cartilage with water under pressure. However, gelatin has a number of market flaws, for example due to recent concerns about bovine spongiform encephalopathy (BSE), or "mad cow disease". This product is of animal origin, which often excludes consumption by people who cannot or do not want to take capsules of this origin.

[0004] As a result, academic and industrial centers have been trying for many years to develop substances that are an alternative to gelatin that could be successfully used in many devices and technologies, including rotary matrices already in use, to produce soft capsules from alternative agents against gelatin.

[0005] For example, Japanese Patent Application Publication No. 61-10508A, Kokai, discloses capsules made from a polysaccharide composition containing at least carrageenan and polyhydric alcohols. Carrageenan can be used fully or partially with other polysaccharides, such as tamarind gum, pectin, gelatin, alginates, agar, furcellaran, cellulose derivatives, carob gum and guar gum. Polyhydric alcohols include sorbitol, glucose, sucrose, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, butanediol and glycerin. Soft capsules are made using concave dies.

[0006] Japanese Patent Application, Kokai Publication No. 63-164858, discloses mixtures of polysaccharides and polyhydric alcohols, with or without basic substances. The broad group of polysaccharides considered useful in this application include natural polysaccharides, e.g. carrageenan, alginic acid, alginate derivatives, agar, carob gum, guar gum, tamarind seed polysaccharides, pectin, xanthan gum, glucomannan, chitin, pullulan and cyclodextin. It has been described that polysaccharides are to be combined with a concentrated aqueous solution of at least one of the following: polyhydric alcohol, sugar alcohol, monosaccharide, disaccharide and oligosaccharide. These mixtures are reported to be useful for making soft capsule shells. Three examples relate to the production of soft capsule shells having a double layer of a mixture with gelatin and a single layer formed from the mixture of the invention with gelatin. No specific carrageenans listed.

[0007] US Patent No. 5089307 discloses heat-sealable, edible films consisting of at least a film layer comprising a water-soluble polysaccharide as the main component, polyhydric alcohol and water. These films are found to be useful as sealing and packaging materials for dried foods, oil foods and the like. Polysaccharides considered useful include alginic acid and its salts (such as sodium salt); furcellaran; carrageenan such as kappa-, iota- and lambda-carrageenans; agar; pectin such as pectins with a high content of methoxy groups and pectins with a low content of methoxy groups; gums such as tamarind seed gum, xanthan gum, guar gum, tara gum, carob gum; pullulan; chitin derivatives such as chitosan; starch such as wheat, corn, potato starch; dextrin; water-soluble edible cellulose derivatives such as carboxymethyl cellulose; and mixtures of the above. The weight ratio of polyhydric alcohol to polysaccharide is preferably from 1: 5 to 1: 1, and the polysaccharide is present in an amount not less than 50% of the total amount of active ingredients. It is not stated whether such films can be used for the production of soft or hard capsules.

[0008] US Patent No. 6331205 discloses viscous aqueous solutions for making soft or hard capsules, containing carrageenan, preferably iota-carrageenan, as the only gelling agent. Iota-, lambda-, mu- and nu-carrageenans have been described as types of carrageenans that may be useful in the present invention, it is reported that they are isolated from a wide variety of seaweed, depending on the extraction method. Plasticizers are disclosed, for example belonging to the class of polyoxy compounds, among others glycerol, sorbitol, maltodextrins, dextrose, mannitol, xylitol, polyoxyethylene glycol from 400 to 6000, natural and semi-synthetic glycerides and their derivatives. It has been found that soft capsules are to be obtained by adaptation of the Scherer method. It was mentioned that the films made from kappa-carrageenans undergo syneresis, which causes problems in the production of hard and soft capsules. There is no description of specific iota-carrageenans, kappakaragens, kappa-2-carrageenans, etc.

[0009] US Patent No. 6214376 discloses gelatinous capsules made from compositions containing water-soluble hydrophilic colloid layers consisting of kappa-carrageenan and plasticizer gel films. It has been reported that soft gelatine capsules are made of kappa-carrageenan as the main gel-forming polymer (at least 50% by weight of gums that form thermoreversible gels or contribute to the formation of thermoreversible gels). Hydrolysed starches, for example maltodextrin, may be added to increase the concentration of solids, facilitate welding and prevent fogging caused by gelling salts. It is noted that the amount of other types of gum, e.g. iota-carrageenan, should be reduced to a minimum, most preferably to less than 0.5% of the total film composition.

[0010] US Patent No. 6340473 requires the use of modified starch whose hydration temperature is less than 90 ° C, and iota-carrageenan for the production of soft capsules by means of a rotary die encapsulating machine. It has been found that the weight ratio of modified starch to iota-carrageenan is extremely important for the production of an appropriate quality film, namely it should be 1.5: 1. According to the authors of the invention, neither iota-carrageenan nor modified starch alone allows obtaining an acceptable quality film suitable for encapsulation. The theory has been put forward that iota-carrageenan acts as a elasticizing agent, thanks to which inelastic modified starch generally acquires elasticity. It was explained that carrageenans are a complex issue, and hundreds of different products with different properties are available on the market. It is reported that Eucheuma spinosum is seaweed that is a source of iota-carrageenan and that not all carrageenans can be used in the invention, for example kappa-carrageenan cannot replace iotacaragen.

[0011] It is known that some film-forming compositions with high solids content and low humidity, which contain, for example, hydrocolloids, form highly viscous solutions, which makes obtaining hydrated films difficult. The present invention relates to a method for obtaining films with high solids content and low humidity from such highly viscous solutions.

[0012] It should be added that many attempts are made to make soft capsules from films with a high solids content and low humidity, for example from the hydrocolloids the difficulties mentioned above have been encountered. Hydrocolloids are known to give high viscosity solutions that are difficult to hydrate sufficiently to form a film in conventional methods for producing soft capsules. The technology presented in the invention therefore allows the production of soft capsules from such films.

SUMMARY OF THE INVENTION [0013] In a first embodiment, the present invention relates to a homogeneous, thermoreversible gel film comprising a film-forming amount of kappa-2-carrageenan and optionally at least one of a plasticizer, second film-forming agent, filler, and pH adjusting agent.

[0014] In a second embodiment, the present invention relates to a method of making gel films comprising the following steps: (i) heating, hydrating, mixing, solubilizing and, optionally, venting the kappa-2-carrageenan composition with optionally at least one of a plasticizer, second film forming agent, filler and pH adjusting agent in a device providing appropriate shear forces, temperature and time stay to create a homogeneous, thermoreversible, molten mixture, wherein the temperature is equal to or above the solubilization temperature of the molten mixture and (ii) cooling the molten mixture to a temperature equal to or lower than the gelation temperature to obtain a gel film.

[0015] In a third embodiment, the present invention relates to soft capsules consisting of walls and an encapsulated substance, the walls of the capsule being the gel films of the present invention, as well as a method for their preparation. This process includes the stages of: (i) heating, hydrating, mixing, solubilizing and, optionally, deaerating the kappa-2-carrageenan composition with optionally at least one of a plasticizer, second film-forming agent, filler, pH adjusting agent in a device providing appropriate shear forces, temperature and time stay to create a homogeneous, molten mixture, wherein the temperature is equal to or above the solubilization temperature of the molten mixture and (ii) making soft capsules directly from the molten mixture or cooling the molten mixture to its gelation temperature or lower, and then making soft capsules therefrom.

[0016] In a fourth embodiment, the present invention relates to solid forms containing a filling material, encapsulated in a homogeneous, thermoreversible gel film according to the present invention, for example hard capsules.

BRIEF DESCRIPTION OF THE DRAWINGS [0017]

Fig. 1 is a flow diagram of the present invention for the production of soft films and capsules using a reactor from Stephan Machinery and an extruder.

Fig. 2 is a flow diagram of the present invention for producing films and soft capsules using the fluid mixer shown in Fig. 3 and an extruder. The diagram shows the film coming out of the extruder and moving to the capsule machine.

Fig. 3 is a side elevational view of a fluid mixer in partial cross section for mixing the first and second liquids with steam that can be used in the process of the present invention.

Fig. 4 is another version of the diagram of Fig. 2 showing the film coming out of the extruder and moving into the encapsulating machine.

Fig. 5 is a schematic of the process of making films and soft capsules using the mixer of Fig. 3, the cooling drum and the encapsulating machine according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION [0018] Carrageenan is a galactan polysaccharide with commercial significance, found in redworms. All carrageenans contain repeating galactose units, connected by alternating glycosidic linkages al-> 3 and β-1- »4, and have a very different number of sulfate groups. Individual types of carrageenan can be distinguished, in part, by the number and location of sulfate groups, as well as the species of seaweed from which they were obtained. For example, iota-carrageenan has a repeating unit of D-galactose-4-sulfate-3,6-anhydro-D-galactose-2-sulfate, resulting in a sulfate ester content of 25% to 34%. Iota-carrageenan can be isolated from Eucheuma denticulatum (also called Spinosum). Kappa-carrageenan has a repeating unit of D7 galactose-4-sulfate-3,6-anhydro-D-galactose and can be obtained from Kappaphycus alvarezii (also called Eucheuma cottonii). In turn, kappa-2-carrageenan, according to R. Falshaw, HJ Bixler and K. Johndro in Structure and Performance of Commercial Kappa-2 Carrageenan Extracts, Food Hydrocolloids 15 (2001), 441-452, and H. Bixler, K. Johndro and R. Falshaw in Kappa-2 carrageenan: structure and performance of commercial extracts II, Food Hydrocolloids 15 (2001), 619-630, is a copolymer containing a number of repeating units of kappa (3,6-anhydrogalactose (3,6-AG)) and repeating iota units (3,6-anhydrogalactose-2-sulfate (3,6-AG-2-S)), covalently bound in the copolymer backbone, and obtained from certain algae Gigartinaceae. The above publication states that such kappa-2-carrageenans have clearly different properties compared to simple mixtures of kappa and iota-carrageenans. Other sources dealing with kappa-2-carrageenan are also discussed in these publications. R. Falshaw, H. Bixler and K. Johndro in Structure and Performance of Commercial Kappa-2 Carrageenan extracts III, Food Hydrocolloids 17 (2003), 129-139 mention kappa-2-carrageenan extracted from Gigartina atropurpurea. Although there has been considerable controversy in the past about the physical nature of kappa-2-carrageenans, in recent studies, for example, those listed directly above, it has been confirmed that kappa-2-carrageenans are copolymers containing repeating kappa and iota units covalently linked (in a defined ratio of groups kappa to iota) in the copolymer backbone, which clearly distinguishes them from physical mixtures of kappa and iota polymers.

[0019] In this document, it is assumed that in kappa-2-carrageenan, the molar ratio of 3.6AG-2-S to 3.6-AG is 25% to 50%, in iota-carrageenan 80% to 100%, and in kappacaragen the molar ratio of 3.6-AG-2-S to 3.6-AG is smaller than for kappa-2-carrageenan. For example, kappa-carrageenan from Eucheuma cottonii, the widely known and used seaweed that is the source of kappa-carrageenan, has a molar ratio of 3.6AG-2-S to 3.6-AG lower than about 10%, while iota-carrageenan from Spinosum, commonly known and used seaweed which is a source of iota-carrageenan, has a molar ratio of 3.6-AG-2-S to 3.6-AG higher than about 85%. This means that in kappa-2-carrageenan, the ratio of kappa repeating units (3,6-AG) to iota repeating units (3,6-AG-2-S) is from 1: 1 to 3: 1, in particular from 1.5: 1 to 3: 1 (the exact value depends on the particular application). The molar ratio of 3,6-AG-2-S groups to 3,6-AG groups in kappa-2-carrageenans is within 25% 50% regardless of their degree of modification and precursor content (e.g. mu and nu repeating units ). It follows from the above that each kappa-2-carrageenan meeting the condition of exhibiting a molar ratio of 3,6-AG-2-S to 3,6-AG components in the range of 25% to 50%, regardless of its degree of modification, remains within the scope of the present invention.

[0020] Kappa-2-carrageenan suitable for use in the present invention may be contained in or obtained by purification or isolation of a number of species of seaweed, for example from the algae family Gigartinaceae, among others Gigartina radula, Gigartina corymbifera, Gigartina skottsbergii, Iridaea cordata, Sarcothalia crispata and Mazzaella laminarioides. The source of kappa-2-carrageenan suitable for use in the present invention is any seaweed that produces kappa-2-carrageenan having a molar ratio of 3,6-AG-2-S to 3,6-AG as described herein. Kappa-2-carrageenan that can be used in this invention may occur naturally in the above-mentioned seaweeds or may be obtained by modifying these seaweeds to increase the number of 3,6-AG-2-S and 3,6-AG moieties in kappa-2caragen relative to their precursors (e.g. 3,6-AG-2-S moieties found in kappa2-carrageenan obtained by modifying its precursor nu as a result of alkali treatment and / or 3,6-AG moieties found in kappa-2-carrageenan obtained by modifying its precursor in as a result of alkali treatment). Methods for obtaining and modifying are well known in the industry, including from quoted publications by Falshaw, Bixler and Johndr. For example, modification of kappa-2-carrageenan may occur during its secretion from certain algae of the Gigartinaceae family as a result of treatment with alkali at elevated temperature. One method of isolation is the complete or partial filtration of insoluble substances from the starting material; You can also use unfiltered material. When the nu and mu precursors in kappa-2-carrageenan are modified to 3,6-AG-2S and 3,6-AG, respectively, such modification may be complete (i.e. 100% of the nu and mu precursors in kappa-2caragen are modified to 3,6-AG-2-S and 3,6-AG, respectively) or less than full (i.e. less than 100% of the precursors nu and mu in kappa -2-carrageenan is modified to 3,6-AG-2-S and 3,6-AG, respectively). It is assumed that in the process of obtaining kappa-2-carrageenan from the above seaweed, there may be small or traces of other carrageenans (e.g. lambda-carrageenans) which can be used together with kappa-2-carrageenans in the present invention.

[0021] One of the surprising discoveries are the properties of kappa-2-carrageenan compared to kappa-carrageenans, iota-carrageenans and simple, dry mixtures of kappa and iotacaragens, which have an identical content of 3,6-AG-2-S. Iota- and kappa-carrageenans are gelling carrageenans, while kappa-2-carrageenans are known to have poor gelling properties - it should be concluded that such gellingly carrageenans will form weak gel films. However, to the surprise of the applicants, it was found that kappa-2-carrageenans form strong gel films.

[0022] Despite the absence of a theoretical foundation, it is generally recognized that the strength of the kappa carrageenan water gel decreases significantly as the 3.6-AG-2-S content increases (e.g. from 1500 g to 300 g in a 1% aqueous solution), which is due to structural interference caused by the presence of additional sulfate esters when aggregating helixes and forming hydrogen bonds between such aggregated helixes. This tendency also occurs in the case of kappa-2 (25% -50%, especially 25% -40% for specific applications, 3,6-AG-2-S groups), while the strength of water gels decreases even to 150 g, which probably results from the variability of the structure. However, iota-carrageenan (e.g. 80% -100% of 3,6-AG-2-S moieties are structurally more structured, thanks to which the spatial structure of such a water gel is more homogeneous, which in turn gives a more durable water gel (as indicated by the breaking load value exceeding 300 g) . Despite the lack of a specific theory, it is believed that the simple physical mixtures of kappa- and iota-carrageenans have a somewhat antagonistic effect on the gel strength, most likely due to the mutual disruption of the ideal gel structures that were formed at different temperatures under cooling. The obtained gel strength values ​​for dry-prepared mixtures of kappa and iota-carrageenan water gels are still significantly higher for the water gel compared to kappa-2-carrageenan. Such antagonism may also be induced by separate hydration and solubilization of kappa- and iota-carrageenans and, while maintaining their solutions above the gelation temperature, homogeneous combination of solutions and pouring or allowing the mixture to cool to initiate gelation. This decrease in gel strength (structural weakness) is even greater when the extract viscosity is reduced (shorter particles) and divalent cations are added. This means that based on traditional gel strength and texture measurements, it would not be expected that kappa-2-carrageenan would be suitable for the production of gel films.

[0023] However, as the authors of the present invention have found, if kappa-2-carrageenan is used to make gel films, it gives a surprising gel strength and mechanical coherence, much higher than expected based on conventional (prior art) studies of molecular structures in for water gels. It also shows full compatibility with traditional film components, including capsule films, e.g. starches, humectants. It is believed that the random, copolymer structure of kappa-2-carrageenan gel in such gel films and film compositions is ideal and contributes to full structural stability from the very beginning of gelation, without the need or tendency to change during or during the film drying process. The structure remains as after gelation, in contrast to the structure of kappa-carrageenan, which then hardens, iota-carrageenan, which is too elastic and stretches, and physical mixtures of kappa and iota (in contrast to kappa-2 copolymers), which are subject to structural disturbances. This unexpected strength of the kappa-2-carrageenan film also allows for the control of the molecular weight of carrageenan in order to better stabilize the technological viscosity and the required film strength during mechanical capsule forming, which allows the process to be carried out with lower water content in poured films and at the same time maintaining other necessary properties foil.

[0024] Kappa-2-carrageenan is used in the present invention in a film-forming amount (e.g. in a quantity that gives the gel film a film strength), which should be distinguished from trace amounts of kappa-2-carrageenan that do not give the film its intrinsic properties. For example, for the gel film according to this invention containing the additional film-forming agents referred to below, the amount of kappa-2-carrageenan forming the film is the amount that gives strength to the entire film. Such film-forming amounts are generally at least 0.5% by weight of dry gel foil, especially from 0.5% to 90%, especially from 0.5% to 50%, preferably from 0.5% to 25%, more precisely from 1, 5% to 25% by weight of dry gel foil, depending on the application.

[0025] The term "homogeneous film" as used herein means a film which, in the eyes of the unaided eye, is visually uniform and free from defects, such as lumps, cracks, the presence of insoluble particles (which should be dissolved), the non-uniform distribution of insoluble particles. Fisheye (mixed liquid and solid phases) or 'gel balls' (uneven gel structure) do not meet the definition of the term 'homogeneous' used in this document.

[0026] The gel films of the present invention are homogeneous, thermoreversible gel films. They can be poured and used in many different applications, as cast films or for further processing.

[0027] The term "thermoreversible film" as used herein means a film that has a melting point. "Melting point", in the description below, means the temperature or range within which the gel film softens or flows.

[0028] The term "gel film" as used herein means a thin membrane or spatial network formed by structured kappa-2-carrageenan. The gel forming substance is characterized by its gelation temperature, i.e. the temperature below which the molten mass of the gel composition must be cooled to form a self-supporting structure. Optionally, the molten mass can be poured hot and allowed to cool as well as dry to increase solids concentration (controlled removal of water) until it forms a gel film. The melting point of the thermoreversible gel film is higher than its gelation temperature.

[0029] The gel film of the present invention preferably contains soluble gelling cations that facilitate the formation of carrageenan structure, i.e. gel formation; they include potassium, sodium and ammonium. These cations may be present in kappa-2-carrageenan or may be added to it from other organic or inorganic sources at various points in the process while maintaining the molten mass above its gelation temperature. These cations having a beneficial effect may be present in an amount less than 50% of the dry weight of kappa-2-carrageenan in the gel foil (together with water). This amount may vary depending on the components present in the system, the desired melting point. [0030] Other soluble cations, e.g. calcium, magnesium, aluminum and chromium, can adversely affect stability, so their amount should be as low as possible, namely lower than 10%, less than 5%, less than 1% on the dry weight of kappa-2-carrageenan in gel foil (together with water). Masking agents (sequestrants) or chelating agents may be added in an appropriate amount to minimize the dissolution of the above cations (and their concentration activity), provided that neither the sequestrant nor the compound resulting from masking will adversely affect the gel system.

[0031] The molecular weight of kappa-2-carrageenan is generally above 100,000 daltons, preferably from 100,000 to 1,000,000, more preferably from 100,000 to 450,000, even more preferably from 100,000 to 350,000, depending on the application.

[0032] In some applications, it is desirable to reduce the gelation temperature of kappa-2-carrageenan. The gelatinized kappa-2-carrageenan system having medium or high molecular weight has a gelation temperature of at least 59 ° C and 35 ° C for the potassium / calcium and sodium forms, respectively. It follows that replacing the potassium cation with a sodium cation is one way to reduce the gelation temperature of kappa-2-carrageenans. It is generally recognized that the gelation temperature does not depend on the molecular weight of kappa-2-carrageenans. Surprisingly, however, applicants have found in their research that in systems with a high solids content of at least 50%, the use of reduced molecular weight kappa-2-carrageenan [e.g. having a viscosity of 19 cP or less, especially less than 10 cP, at 75 ° C in 0.10 molar sodium chloride solution containing 1.5% carrageenan with reduced molecular weight, by weight relative to the total weight of the solution; viscosity testing can be performed using a Brookfield LVF viscometer (Brookfield Engineering Laboratories, Inc.) using spindle No. 1 at 60 rpm and determining the viscosity after six revolutions] can further reduce the gelation temperature of kappa-2-carrageenan, for example from 59 ° C to 57 ° C for the potassium / calcium form and 35 ° C to 25 ° C for the sodium form. Reducing the gelation temperature of the structure produced by kappa-2-carrageenan may have positive effects on the gel film technology of the present invention, for example in the production of soft capsules, hard capsules and other solid forms, by reducing the amount of heat consumed in the production process and minimizing the residual stress in dried film.

[0033] The homogeneous, thermoreversible gel film of the present invention may contain at least one of a plasticizer, a second film forming agent, a filler and a pH adjusting agent. The ingredients added to the gel foil and their amounts may vary depending on the required use of the gel foil with kappa-2-carrageenan.

[0034] Examples of such a plasticizer may be polyols such as glycerin, sorbitol, maltitol, lactitol, corn starch, fructose, polydextrose, solubilized oil as well as polyalkylene glycol, among others propylene glycol and polyethylene glycol. The amount of plasticizer may vary depending on the use of the gel film and its desired flexibility. For example, such plasticizers can be used, in general, in an amount of at least 5%, preferably at least 10%, more preferably at least 20%, most preferably at least 30%, by weight of all ingredients, including water, in a dry film, if a gel film having greater flexibility is desired, for example a film for producing soft capsules. In other applications, such as hard capsules, in which less flexible films are required, the plasticizer may be present in an amount of from 0% to 20% by weight relative to all the components of the dry film, so it is possible that the gel film according to the invention will not contain a plasticizer at all.

[0035] Examples of additional film forming agents that can be used in the present invention include at least one substance among starch, starch hydrolyzate, starch derivative, cellulose gum, hydrocolloid, alkyl cellulose ether or modified alkyl cellulose ether. Examples of hydrocolloids include at least one of kappa-carrageenan; iota-carrageenan; kappa-carrageenan and iota-carrageenan with reduced molecular weight [e.g. having a viscosity of 19 cP or less, especially less than 10 cP, at 75 ° C when measured in 0.10 molar sodium chloride solution containing 1.5% (based on the total solution weight) reduced molecular weight carrageenan; viscosity testing can be carried out using a Brookfield LVF viscometer (Brookfield Engineering Laboratories, Inc.) using spindle # 1 at 60 rpm and determine the viscosity after six revolutions] and their less than fully modified variants; alginates, including potassium alginate, sodium alginate, ammonium alginate and propylene glycol alginate; Polymannan rubbers (e.g. with a viscosity of less than about 1000 mPs, measured at a concentration of 1% by weight in water, at a temperature of 25 ° C), for example, low viscosity guar gum; pullulan, gellan (including high and low acyl group gellan); dextran; pectin and combinations thereof. An example of an alkyl cellulose ether that can be used in the present invention is hydroxyethyl cellulose. Examples of modified alkyl cellulose ethers that can be used in this invention include hydroxypropyl cellulose and hydroxypropyl methyl cellulose. Kappa-2-carrageenan may be the only film-forming agent in the gel foil. If the gel films of the invention contain additional film-forming agents, kappa-2-carrageenan can be present in an amount of at least 10%, at least 20%, at least 50% or at least 80% by weight in the total amount of film-forming agents in the dry gel film.

[0036] Dry film is a material formed from film poured after controlled removal of water. Combinations of ingredients, e.g., kappa-2-carrageenan and, optionally, starch, polyol and process water, are dispersed, hydrated, solubilized and, optionally, vented as part of the process options described herein. The resulting homogeneous mass is poured or molded at the desired solids content (necessary to obtain the intended end product). The poured material is created under the influence of gravitational or forced forces and is then either immediately used (for example, soft gel capsules are produced), or the poured mass is further processed by various methods of uniform and controlled removal of water until the desired humidity is obtained. Controlled removal of water from the poured material further increases the strength of the homogeneous film and orientation of its components into a structure with a higher density, which can further improve the strength parameters of the film. Water removal is limited to unbound water on the surface of the molecules of individual hydrocolloid and carbohydrate components. The poured film is dried when it no longer loses weight after being subjected to various drying methods used in the dehydration and / or dehydration process. Reducing the water content to a constant level also gives the film stability, and possibly its components (if they are embedded, surrounded, sealed, etc.), because the water activity is also reduced in this process.

[0037] Examples of fillers include non-colloidal cellulose (of plant origin), microcrystalline cellulose (of plant origin), microcrystalline starch, modified and unmodified starch, derivatives and starch fractions, inulin, starch hydrolysates, sugar, corn syrup and polydextrose. The term "modified starch" includes, in the present description and in the claims, hydroxypropylated starches, acid thinned starches and the like. Modified starches that can be used in the present invention include, but are not limited to, Pure-Cote® B760, B790, B793, B795, M250 and Ml80, PureDent B890 and Pure-Set B965, all available from Grain Processing Corporation of Muscatine in Iowa, and C AraTex 75701, available from Cerestar, Inc. Examples of starch hydrolysates include maltodextrin, also known as dextrin. Unmodified starches, for example potato starch, may also increase the strength of the film when combined with hydrocolloids, which is within the scope of the invention. Modified starches are generally products obtained by chemical treatment of starch, for example starches treated with acids or enzymes, oxidized starches, cross-linked starches and other starch derivatives. It is preferred that the modified starches are derivatized by modifying the side chains with hydrophilic or hydrophobic groups, thus creating a more complex structure with strong interactions between the side chains.

[0038] The amount of filler to be used in the present invention is usually from 0% to 20% by weight in dry film, however, if desired it can be higher, for example at least 20% or even at least 30% by weight in dry film.

[0039] It should be noted that starch and its derivatives and hydrolysates can be multifunctional, that is, in addition to being a filler, they can also act as a second film-forming agent. If added as fillers and additional film forming agents, it is generally in an amount of at least 10%, preferably at least 20%, more preferably at least 30% by weight in dry gel film, depending on the application (e.g. in soft capsules).

[0040] The pH adjusting agents that can be used in the present invention are alkaline substances, among others hydroxides, carbonates, citrates and phosphates, and mixtures and salts thereof (e.g. sodium citrate). The pH adjusting agent can be selected as a source of additional, preferably acting cations (e.g., potassium or sodium), and in some compositions can be used to increase the stability of the gel film. The amount of pH adjusting agent is typically from 0% to 4%, in particular from 0% to 2%.

[0041] The gel films of the invention may also contain coloring and flavoring additives, for example sugar, corn syrup, fructose, sucrose, aspartame, sucralose, sorbitol, mannitol, maltitol, regardless of whether other ingredients such as plasticizers, fillers are present , additional foaming agents, etc. In one embodiment, the gel film of the invention contains kappa-2-carrageenan, flavoring and water, in a system with a high solids content, namely exceeding 50%, 60%, 65%, 75%, 80%, 85%, 90 %.

[0042] Dry gel films (e.g., 80% or more solids) according to the present invention have been found to have a breaking strength of at least 1500 g, at least 2500 g, at least 4000 g, at least 5000 g and at least 6000 g as determined by the Texture Analyzer TA-108S Mini Film Test Rig. At lower solids content, the gel films were found to have a breaking strength of at least 50 g, at least 100 g, at least 200 g, at least 500 g, at least 1000 g, as determined in a similar manner.

[0043] The films of the present invention have been found to have a solids content of at least 50%, at least 60%, at least 70%, at least 80% and at least 90% relative to all components of the gel film. It is assumed that 15%, 10% or 5% of water can remain strongly bound to solids in a dry gel film.

[0044] The thickness of the dry film, which is usually used in the production of soft capsules, is in the range of 0.5 to 3.0 mm, in particular 0.8 to 1.2 mm.

[0045] It is possible that the gel films of the present invention may contain non-thermoreversible gums. However, so that they do not adversely affect the homogeneous and thermoreversible nature of the gel films of the invention, non-thermoreversible gums should be present in an amount less than 50% by weight relative to kappa-2-carrageenan, preferably less than 40%, more preferably less than 30%. Examples of such non-thermo-reversible gums are cross-linked gums, including pectins and alginates cured (e.g. cross-linked) with calcium. Alginates and calcium-reacting pectins, as well as their less purified forms, are considered thermoreversible gums in the absence of divalent cations. Other non-thermoreversible gums, e.g. tragacanth, contribute to the thermoreversibility of kappa-2-carrageenan - due to the absorption of water in their structure, kappa-2-carrageenan forms a denser spatial structure, because solubilization occurs in less water, giving the same effect , like increasing the amount of kappa-2-carrageenan without the help of film-forming agents. Additional film-forming agents, e.g. polymannans, can form continuous networks, alone or synergistically, together with other components during the activation and pouring process.

[0046] The kappa-2-carrageenan gel films of the present invention are typically made by a process using apparatus that provides sufficiently high shear forces, a temperature higher than the gelation temperature, and a sufficiently long residence time to obtain a homogeneous, molten mass of the composition and gel formation after cooling. Such devices include, but are not limited to, Ross mixers, Stephan reactors, conventional jet cookers, extruders, and a fluid mixer illustrated in

Fig. 3. Ross mixers, Stephan reactors, extruders and conventional jet cookers are commercially available. Before cooling, the molten mass can be introduced into at least one of the pump, mixer or volatile removal apparatus. An example of a device that performs any of these functions is an extruder. The extruded molten mass can also be directed to a film forming or shaping device (e.g. to the distribution chamber used in the capsule making plant), which facilitates uniform casting of a continuous film, or onto a matrix that allows direct film formation or molding of a molten mass supplied from the feeding device. It should be ensured that the molten mass is kept above the start point of the flow restriction and gel structure formation.

To ensure the flow of molten mass until the desired gel film formation has started on the casting rollers, or at another film forming point, for example in an extruder (film making device, with limited flow) or matrix, insulated transmission pipes (hoses) or pre-heated (to maintain the right temperature). Additional technological solutions (e.g. preheating of the dosing / numbered head, present in Ross apparatus) may consist in forcing (pressure) the flow of molten mass through the above-mentioned transport lines. Additional insulation with a Teflon disk, which is initially placed on the surface of the molten mass immediately after removing the mixing device, can help maintain the temperature of the molten mass. In addition, the supply lines can be introduced into the thermally controlled (pouring) chambers of the molten mass feeder, located on the capsule, or directly to these chambers, or by optionally modifying the feeder chambers by adding a housing or cover on the upper half, facilitating maintaining the temperature of the molten mass in the feeder chamber . reducing water loss and maintaining uniform (central) chamber filling during the long process of making capsule films. It should be understood that other methods for maintaining the temperature of the molten mass can be used to make such films. These include, but are not limited to, extrusion of molten mass through dies or film openings that can be: immediately fed into the capsule machine, stored for the necessary time at a temperature that maintains the appropriate (for capsule production) film properties, or dried until obtained adequate humidity, structure and concentration of solids. Such dry films have the property of reabsorbing water (which is fed by any method) to the entire structure of the gel film; they can be rehydrated if necessary, for example to produce soft capsules or other solid forms. Water is introduced into the film in an amount necessary to achieve adequate humidity and texture / strength that will allow the film to be fed into a soft capsule making machine.

[0047] The term "fluid mixer" as used herein means the apparatus of Figure 3. Figure 3 shows the fluid mixer 10. Fluid mixer 10 is designed to mix vapor 2 with the first liquid or suspension 4 and with the second liquid or suspension 6 to obtain a mixture of molten mass or suspension 8.

[0048] The fluid mixer 10 consists of a first housing 20 having a first inlet 22 through which steam 2 enters the housing 22, the end 24 of the nozzle from which steam 2 exits the housing 20, and a valve or nozzle stem 26 located at the end of 24 nozzles. The actuator arm 30 reaches the first housing 20 to control the flow rate or outlet pressure of the first fluid 2 at the end 24 of the nozzle. The actuator 30 may be of the type manufactured by the American company Fisher Controls.

[0049] The fluid mixer 10 further includes a second mixing housing 40 connected to the first housing 20 at the end 24 of the nozzle of the first housing 20. The second housing 40 includes a second inlet fitting 42, through which the first liquid 4 enters the second housing 40, and a third fitting inlet 44 through which the second liquid 6 enters the second housing 40. Inlet ports 42 and 44 are located below the first inlet port 22. As shown in Fig. 3, the second inlet fitting 42 and the third inlet fitting 44 are in a common plane and are located on opposite sides, preferably exactly opposite (i.e. at an angle of 180 °) to the central Y axis of the mixer 10. The second housing 40 is a substantially cylindrical mixing chamber 52, which in turn is a flow channel running along the axis of the mixing chamber 52 from inlet 54 to outlet 56. The nozzle valve 26 is moved by the actuator 30 between the position in the seat and the position above the seat at the inlet 54 to regulate the steam flow 2 into the mixing chamber 52.

[0050] The end 24 of the nozzle in the first housing 20 directs steam 2 to the inlet 54 of the mixing chamber 52. The second inlet stub 42 and the third inlet stub 44 radially direct the first liquid 4 and the second liquid 6, respectively, to the mixing chamber 52. Steam 2, first liquid 4 and second liquid 6 are mixed in chamber 52 to form a molten mass or mixture 8 that leaves the chamber. The molten mass 8 can then be formed into a shaped article or formed into a film, for example by pouring the mixture 8 onto a cooling drum or by passing it through an extruder.

[0051] Fig. 4 shows an installation 100 for the production of films and capsules, together with the above-described fluid mixer 10, which includes a film production module 60 for preparing and delivering film 9, and a capsule maker 80 for producing capsules 89. Module 60 includes: fluid mixer 10; a first liquid supply system 62 that serves to feed the first liquid 4 to the mixer 10; a second liquid supply system 64 that serves to feed the second liquid 6 to the mixer 10; a feed path 70 for providing a slurry mixture that serves to feed the molten mass or slurry mixture 8 from the mixer 8 to the shaping device; optionally an extruder 73 along a feed path 70 for delivering a mixture that extrudes the mixture 8 into film 9; a capsule machine 80 that is used to make capsules 89; and a conveyor belt 90 that serves to transport the filled capsules 90 to the next stage of the process, which can be drying or packaging. The extruder 73 may be of the type manufactured by Wenger or Clextrel.

[0052] Capsule 80 can be a conventional rotary matrix encapsulating device of the type manufactured by RP Scherer Technologies of Paradise Valley, Nevada. As shown in Fig. 4, the capsule machine 80 has a reservoir 82 for encapsulating material that houses an article 81 to be encapsulated. Product 81 can be liquid, semi-liquid or powder pharmaceutical products, vitamins, food supplements, paint spheres, pigments, active ingredients for agricultural use and weighed food additives. The capsule machine 80 can cooperate with one or more rollers 77, 77 'and 78, 78' so that the films 9, 9 'can be drawn into it. The film 9 is introduced between the heating block 86 and the roll matrix 88. Small areas of the film 9 are vacuum sucked into the cavities in the surface of the rotary matrix 88. A suitable amount of the encapsulated product 81 is fed into each of the cavities thus formed in the film 9. The rotational movement of the matrices 88, 88 'then causes the films 9, 9 to be joined together. 'as a result of squeezing them between rotating dies 88, 88'. The filled capsules 89 fall into the containers 87, 87 ', from which they fall onto the conveyor 90, transporting them to the drying and packaging place.

[0053] The plant 100a for making capsules shown in Fig. 5 is similar to that shown in Fig. 4, with the reference numerals of the elements in both figures corresponding to each other. However, in Fig. 5, the film production module 60a includes an optional melt distribution chamber 72 and an optional cooling drum or pouring drum 74, instead of the extruder 73 from the installation in Fig. 4. The installation 100a includes a fluid mixer 10 and a feed path 70 for supplying a slurry mixture that serves to collect the slurry mixture 8 from the mixer and direct it to the distribution chamber 72. From the distribution chamber 72, the mixture 8 is poured evenly onto the drum 74 on which it forms the film 9 will cool as the mixture cools

8. The film 9 is then introduced into the encapsulating machine 80. The film 9 'should be made in the same way as the film 9, in an analogous film production module (not shown).

[0054] The fluid mixer 10 is adapted to make a mixture for obtaining a film, especially an edible film, suitable for producing edible capsules or strips. Incompatible film components are generally placed in various liquid inlet streams so that such incompatible components come into contact with each other for the first time in contact with the injected vapor in the mixing chamber 52. Although Fig. 3 shows steam inlet ports and first and second liquids, one or more additional ports can be used for one or more additional liquids. Preferably, the housings 20, 40 and other components of the fluid mixer 10 are made of high-grade stainless steel.

[0055] As another aspect of the invention, it should be noted that the molten mass need not necessarily achieve homogeneity in step (i). This means that the homogeneity of the molten mass can be achieved before or after introducing the molten composition into at least one device among the mixer, pump, and volatile component removal apparatus; provided that the molten mass is homogeneous before gelation.

[0056] Since the gel films of the present invention have been found to have a dry film strength of at least 2500 g, they are well suited to the production of soft capsules. In this regard, the invention also relates to soft capsules made from the homogeneous, thermoreversible gel films of kappa-2-carrageenan according to this invention, as well as methods of producing such soft capsules.

[0057] The method for making soft capsules with kappa-2-carrageenan gel films according to the invention involves the use of any conventional encapsulation device, including a conventional rotary die or concave die matrix device. For example, after producing the molten mass of the present invention , it can be poured onto drums, cooled, and then fed between rotary encapsulation matrices in which the films are reheated, filled, welded and cut. A good description of such a conventional process is found in patent application WO 98/42294. Alternatively, and as an advantage of the present invention compared to conventional methods for producing soft capsules, the use of the high shear device described above allows proper hydration of the molten mass, pouring it onto cooling drums, and then entering into a conventional capsule machine for filling, welding and cutting. This continuous type process can be used to eliminate the stage in which it is necessary to re-heat completely gelled and cooled films. The above process using rotary matrices can be used to produce soft capsules having any desired shape.

[0058] The materials for filling soft capsules can be any substances usually placed therein using the above rotary matrix method, including pharmaceutical, nutraceutical, veterinary ingredients, ingredients used in agriculture or industry, food, cosmetics, personal care products; they may be in the form of liquids, solids, suspensions, etc.

[0059] The invention also relates to a solid form in the form of a filling encapsulated in a homogeneous, thermoreversible gel film according to this invention. One type of solid form is a hard capsule. Hard capsules, as used herein, are solid forms that are commonly produced, for example in the pharmaceutical industry. Traditional technology produces two halves of a shell, in which a filling material, usually a powder, is placed, after which the two halves are joined together - this creates a hard capsule. One typical method for making such capsules is to immerse metal pins or rods in the molten mass of the present invention, around which a gel film is then formed. The foils formed in this way are dried and then removed from the pins (rods). These technologies are well known in the industry as methods of producing hard capsules. The materials for filling them can be any materials commonly used in such dosage forms. In general, the filler materials may be liquids (including emulsions) or solids such as powders. Such material may be pharmaceutical, nutraceutical, veterinary, cosmetic, agricultural ingredient, food etc.

[0060] In solid form, a powder, tablet, dragee, microcapsule or capsule can be encapsulated according to known methods. For example, encapsulating a hard capsule with the gel film of this invention would allow it to be sealed and / or tamper-proof.

[0061] The gel foil may also be used to modify the dissolution profile of the dosage form. For example, the gel films of the invention may contain additional ingredients that give solid dosage forms the property of immediate, delayed, controlled, enteral release or upon activation by a particular event, condition or process.

Definitions for the terms "immediate release", "delayed release" and "elimination" are given in the American Pharmacopoeia; they are incorporated herein by reference.

[0062] In the following examples, the present invention will be discussed in more detail, however, it should be understood that it is not limited thereto. Unless otherwise stated, all parts, percentages, ratios and the like are by weight.

EXAMPLES [0063] Unless otherwise indicated, the following procedures were used to obtain and evaluate the materials and films of Examples 1-4. The universal reactor Stephan UMC 5 is a laboratory mixing device that provides mixing with sufficiently high shear forces, heating and deaeration of preparations that were poured in the form of foil in the laboratory. The correct batch size for the Stephan UMC 5 reactor was 1500 grams.

[0064] An aqueous starch suspension was prepared by dissolving salts / buffers and pH regulators in deionized water. Starch and / or maltodextrin (M100) were added and mixed until dissolved or dispersed. Pure-Cote® B760 and B790 starch is sold by Grain Processing Corporation of Muscatine, Iowa.

[0065] The hydrocolloid mixture was prepared in the Stephan UMC 5 reactor, first mixing the plasticizers until homogeneous and then adding the pre-mixed dry hydrocolloids in portions, mixing for about 30 seconds at 200 rpm after each addition. The plasticizers were Sorbitol Special and glycerin. Sorbitol Special is an aqueous solution of sorbitol and sorbitol anhydrides, with a solids content of 76%, supplied by SPI Polyols, Inc. (New Castle, Delaware).

[0066] A starch suspension was added to the non-aqueous hydrocolloid mixture and mixed for 5 minutes at 300 rpm. The mechanical stirring speed was increased to 2100 rpm and the mixture was heated to 85 ° C to 95 ° C with stirring. After reaching the target temperature, stirring was continued for 30 minutes, after which the sample was kept under reduced pressure (50-60 bar), still stirring for another 45 minutes.

[0067] When the time of holding under "vacuum" at this temperature had elapsed, the sample was poured into a heated glass jar with a wide opening and a capacity of about one liter. Temperature and pH were recorded. Viscosity was measured in a hot sample using a Brookfield LVF viscometer.

[0068] A small portion of the sample was separated and cooled, usually overnight, before measuring the gel / liquid properties and solids content using an Atago E series hand refractometer (Gardco, Pompano Beach, Florida). The melting (liquefaction) temperature was determined by placing a small fragment of the cooled gel on a wire support in a test tube in such a way that the fragment did not touch the tube wall. The tube was covered with aluminum foil with a small hole that enabled the gel temperature to be measured using a Tempermeter digital probe. The tube was immersed in a heating bath so that the fragment was below the surface of hot water at about 100 ° C. For samples whose melting point was above 90 ° C, a silicone oil bath was used. The melting point was recorded when the gelled sample began to look wet, soft and could be mixed (temperature range recorded). After liquefaction of the sample, the tube was transferred to a second beaker containing cold tap water (15 ° C). A temperature probe was used to record the temperature as the sample cooled, and to check the surface of the sample to determine if gelation had begun. The gelation temperature was the temperature at cooling at which the sample stopped flowing and filled the cavity left by the probe.

[0069] The hot sample was then spread using a rod applicator, in which the gap was set to obtain a clearance of 3 mm, over 177x177x5 mm metal plates onto which PAM (lecithin) had previously been sprayed to facilitate removal of the film material. The gel-coated plates were covered to prevent water loss from the poured film. The poured films were usually cooled (below 8 ° C) for at least half an hour before testing. Cooling is not necessary to form a film. Dried film strips were prepared by drying the coated plates at 40 ° C in a fan oven (forced air). Films dried for 2 hours at 40 ° C had a moderate solids content of about 60%, and films dried overnight at 40 ° C had a solids content of 80% or higher. The properties of the samples were measured at room temperature (about 20 ° C) unless otherwise stated. The percentage solids content in the dried film was calculated based on the weight difference between the poured film and the dried film, using recipe data determining the solids content of the poured film. The breaking load for poured and dried film strips was determined using the Texture Analyzer TA-108S Mini Film Test Rig for testing the strength of the film.

[0070] Unless otherwise specified, Maltrin Ml 00 was obtained from Grain Processing Corporation, Pure-Cote B760 starch from Grain Processing Corporation, Sorbitol Special at SPI Polyols and glycerin at VWR (quality in accordance with European Pharmacopoeia and / or American Pharmacopoeia).

Example 1 [0071] As indicated below, Cgn A carrageenan was obtained, after alkali treatment and clarification, as an extract from Gigartina skottsbergii, plants usually haploid (gametophytes), and isolated by precipitation with alcohol. In addition, small amounts (less than 5% total) of lambda- and theta-carrageenans from diploid plants (tetrasporophytes) were found.

[0072] Cgn B carrageenan was obtained by dissolving Cgn A in water, then it was precipitated with alcohol and dried. Samples of different molecular weights were obtained by reacting dissolved carrageenan with an oxidant to obtain Cgn CF. After the oxidation step and before the alcohol precipitation, sodium hydroxide was added to the Cgn CE samples to adjust the pH of the resulting product. The properties of kappa-2-carrageenans are shown in Table I. The viscosity of the aqueous solution at a solids content of 1.5 wt. measured in

75 ° C using a Brookfield LVF viscometer using appropriate speeds and spindles. Properties of 2% water gels prepared using 2 wt. samples Cgn AF (No. 1) without the addition of cations, (No. 2) with the addition of 0.2 wt. KC1 and (No. 3) with the addition of 0.2% KC1 and 0.2% CaCb, respectively, were determined using a texture analyzer. The gels were tested at 25 ° C, recording the breaking load (in grams) and penetration ( in centimeters).

[0073] The following Cgn AF are examples of kappa-2-carrageenans that can be used in the present invention.

Table I: Properties of kappa-2-carrageenans AF

<td></td><td>Cgn A.</td><td>CgnB</td><td>CgnC</td><td>CgnD</td><td>CgnE</td><td>CgnF</td>

<td>Oxidation test</td><td>no</td><td>no</td><td>Yes</td><td>Yes</td><td>Yes</td><td>Yes</td>

<td>Mg,%</td><td> 0,11</td><td> 0,34</td><td> 0,19</td><td> 0,19</td><td> 0,19</td><td> 0,19</td>

<td>Ca,%</td><td> 0,34</td><td> 0,29</td><td> 0,34</td><td> 0,39</td><td> 0,52</td><td> 0,40</td>

<td>K%</td><td> 12,9</td><td> 8,46</td><td> 8,59</td><td> 8,87</td><td> 8,74</td><td> 8,95</td>

<td>Na,%</td><td> 0,22</td><td> 0,42</td><td> 0,51</td><td> 0,57</td><td> 0,65</td><td> 0,38</td>

<td>viscosity, mPs *</td><td> 175</td><td> 144</td><td> 48</td><td> 24</td><td> 14</td><td> 11</td>

<td>pH</td><td> 9,4</td><td> 9,42</td><td> 8,93</td><td> 9,03</td><td> 9,16</td><td> 6,7</td>

<td>2% water gel</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td> 211</td><td> 38</td><td> 21</td><td> 18</td><td> 11</td><td> 12</td>

<td>penetration (cm)</td><td> 7,4</td><td> 13,9</td><td> 11,5</td><td> 9,0</td><td> 7,8</td><td> 16,1</td>

<td>Water gel (KC1) 2%</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>breaking load, (g)</td><td> 308</td><td> 162</td><td> 126</td><td> 107</td><td> 70</td><td> 51</td>

<td>penetration (cm)</td><td> 7,4</td><td> 9,9</td><td> 7,8</td><td> 7,6</td><td> 7,3</td><td> 6,1</td>

<td>Water gel tKCl + CaCb) 2%</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>breaking load, (g)</td><td> 487</td><td> 349</td><td> 514</td><td> 445</td><td> 356</td><td> 158</td>

<td>penetration (cm)</td><td> 3,6</td><td> 3,1</td><td> 6,4</td><td> 5,3</td><td> 5,0</td><td> 1,7</td>

* viscosity measured at 1.5% solids in deionized water at 75 ° C [0074] Cgn D and E carrageenans were poured in the form of a film. The composition of the charges and the properties of the foil are shown in Table II. It is believed that all recipes are within the scope of the present invention, although some may be more advantageous than others for a given application.

Table II Composition of charges with kappa-2-carrageenans and foil properties

<td></td><td>Example 1-1</td><td>Example 1-2</td><td>Example 1-3</td><td>Example 1-4</td>

<td>Ingredients (g)</td><td></td><td></td><td></td><td></td>

<td>water</td><td> 834,7</td><td> 834,7</td><td> 666</td><td> 497,4</td>

<td>CgnD</td><td> 0</td><td> 75</td><td> 75</td><td> 75</td>

<td>CgnE</td><td> 75</td><td> 0</td><td> 0</td><td> 0</td>

<td>M-100</td><td> 227,3</td><td> 227,3</td><td> 292,3</td><td> 357,2</td>

<td>sorbitol SP</td><td> 272,2</td><td> 272,2</td><td> 349,9</td><td> 427,7</td>

<td>glycerine</td><td> 90,8</td><td> 90,8</td><td> 116,8</td><td> 142,7</td>

<td colspan="5"></td>

<td>temperature, ° C *</td><td> 81,1</td><td> 82</td><td> 85</td><td> 92</td>

<td>viscosity, mPa s *</td><td> 4000</td><td> 13 700</td><td> 22 350</td><td> &gt; 50 000</td>

<td>solids (estimated)</td><td> 40,1%</td><td> 40,1%</td><td> 50,1%</td><td> 60,0</td>

<td>gelation, ° C</td><td> 55-57</td><td> 54-55</td><td> 62</td><td> 77-78</td>

<td>Melting point, ° C</td><td> 73-75</td><td> 77-80</td><td> 85</td><td> 90-92</td>

<td colspan="5">in the form of poured foil</td>

<td>breaking load, G</td><td> 312</td><td> 318</td><td> 404</td><td> 476</td>

<td>dried foil (solids 80% estimated) (16 hours at 40 ° C)</td><td></td><td></td><td></td><td></td>

<td>average film thickness (mm)</td><td> 1,5</td><td> 1,0</td><td> 0,87</td><td> 1,1</td>

<td>breaking load (g)</td><td> 5755</td><td> 5220</td><td> 5613</td><td> 3218</td>

<td colspan="5">* temperature and viscosity of the molten mass before pouring</td>

[0075] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some of them were stronger than others.

[0076] The above table shows that in example 1-2 and example 1-1 the viscosity of the molten mass at the process temperature (13,700 mPa si 4,000 mPa s, respectively) was regulated by reducing the molecular weight Cgn D to Cgn E (expressed as a viscosity of 24 mPa si 14 mPa s, respectively), with little effect on the properties of the film.

[0077] The melting point of the poured material increased (examples 1-2, 1-3 and 1-4) as the solids content of the formulation increased. In examples 1-2, 1-3 and 1-4, the gelation temperature increased as the solids content increased until it approached the temperature of the molten mass. Pre-cast gelation, as indicated by the reduced gel strength of the poured film and the high melt viscosity (&gt; 50,000 mPa) in Example 1-4, is due to the fact that the gel temperature was close to that of the molten mass. This means that at this stage of the process the molten mass temperature should be kept above the gelation temperature if stronger films are needed. Mixing below the gelation temperature breaks the gel structure and reduces strength. The right process equipment hydrates sufficiently, mix homogeneously, and then easily transports the molten mass for further processing, in the same form or for other operations such as shaping or pouring of the film.

Example 2 [0078] Kappa-2-carrageenan was obtained, after treatment with alkali and clarification, as an extract from a mixture of Gigartina skottsbergii and Sarcothalia crispata, usually haploid plants (gametophytes). About 10-20% (total) of lambdai theta-carrageenans from diploid plants (tetrasporophytes) were also found. After isolation of the extract, ion exchange was carried out to obtain kappa-2-carrageenan with a low content of divalent cations. The properties of kappa-2-carrageenans with a low content of divalent cations (Cgn GJ) are shown in Table III. Cgn GJ is considered to fall within the scope of the invention.

<td></td><td>CgnG</td><td>CgnH</td><td>CgnI</td><td>Cgn J</td>

<td>cation exchange</td><td>Yes</td><td>Yes</td><td>Yes</td><td>Yes</td>

<td>Mg,%</td><td> 0,07</td><td> 0,02</td><td> 0,03</td><td> 0,05</td>

<td>Ca,%</td><td> 0,06</td><td> 0,01</td><td> 0,16</td><td> 0,15</td>

<td>K%</td><td> 2,19</td><td> 1,00</td><td> 0,00</td><td> 0,67</td>

<td>Na,%</td><td> 5,12</td><td> 7,70</td><td> 6,90</td><td> 7,40</td>

<td>viscosity, mPs</td><td> 6</td><td> 18</td><td> 45</td><td> 98</td>

<td>viscosity, mPs *</td><td></td><td> 9</td><td> 20</td><td> 41</td>

<td>pH</td><td> 8,12</td><td> 8,7</td><td> 9,6</td><td> 10,1</td>

<td>water gel, 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load, (g)</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td>

<td>water gel (KCl) 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td> 0</td><td> 13</td><td> 29</td><td> 38</td>

<td>water gel (KCl + CaCl₂), 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td> 30</td><td> 93</td><td> 112</td><td> 181</td>

* Measurements of carrageenan Η, I and J were carried out at 75 ° C in 0.10 mole solution of sodium chloride with kappa-2-carrageenan with a solids content of 1.5%.

[0079] The composition of the kappa-2-carrageenan feeds with a low content of divalent cations, according to Cgn GJ samples, and the properties of the corresponding films are shown in Table IV. It is believed that all of the following recipes fall within the scope of the present invention, although some may be more favorable than others for a given application.

Table IV: Composition of feeds with kappa-2-carrageenans with a low content of divalent cations and film properties

<td></td><td>Example 2-1</td><td>Example 2-2</td><td>Example 2-3</td><td>Example 2-4</td>

<td>Ingredients, (g)</td><td></td><td></td><td></td><td></td>

<td>water</td><td> 834,7</td><td> 834,7</td><td> 834,7</td><td> 834,7</td>

<td>CgnJ</td><td> 75</td><td> 0</td><td> 75</td><td> 75</td>

<td>CgnI</td><td> 0</td><td> 75</td><td> 0</td><td> 0</td>

<td>KCI</td><td> 0</td><td> 0</td><td> 9,0</td><td> 9,0</td>

<td>starch B790</td><td> 0</td><td> 0</td><td> 0</td><td> 227,3</td>

<td>M-100</td><td> 227,3</td><td> 227,3</td><td> 227,3</td><td> 0</td>

<td>sorbitol SP</td><td> 274,9</td><td> 274,9</td><td> 274,9</td><td> 274,9</td>

<td>glycerine</td><td> 91,7</td><td> 91,7</td><td> 91,7</td><td> 91,7</td>

<td colspan="5"></td>

<td>temperature, ° C *</td><td> 89</td><td> 87</td><td> 87</td><td> 87</td>

<td>viscosity, mPa s *</td><td> 5800</td><td> 5800</td><td> 6250</td><td> 10300</td>

<td>solids (estimated)</td><td> 40%</td><td> 40%</td><td> 41%</td><td> 40%</td>

<td>gelation, ° C</td><td> 35</td><td> 31</td><td> 52</td><td> 48</td>

<td>Melting point, ° C</td><td>45M8</td><td> 43</td><td> 66-71</td><td> 70</td>

<td colspan="5">in the form of poured foil</td>

<td>breaking load (g)</td><td> &lt;40</td><td> &lt;40</td><td> 281</td><td> 237</td>

<td colspan="5">in the form of dried foil</td>

<td colspan="5">(solids estimated ~ 80%)</td>

<td>average film thickness (mm)</td><td> -</td><td> -</td><td> 0,97</td><td> 0,88</td>

<td>breaking load (g)</td><td> 3468</td><td> 3697</td><td> 3236</td><td> 7603</td>

<td colspan="5">* temperature and viscosity of the molten mass before pouring</td>

[0080] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

[0081] Kappa-2-carrageenans in which ion exchange (I and J) was carried out, in combination with polyols and maltodextrin (as filler) gave a relatively weaker cast gel film, with a minimum breaking strength at 40% solids content. It is believed that this is due to the insufficient amount of potassium cations that are needed to better stimulate carrageenan double helix formation (i.e. gelation) at a temperature that allows carrageenan to be the main structure-building agent. Examples 2-1 and 2-2 are gel films having a relatively low melting and gelation temperature. Although the gelation potential is not maximized (due to low potassium levels), the films of examples 2-1 and 2-2 show a breaking strength of 3468 and 3697, respectively. Example 2-3 demonstrates the effect of adding potassium ions to the structure formed by kappa-2-carrageenan in Cgn J. The poured film, although soft, was strong enough to be removed from the casting plate. Structure building by Cgn J after the addition of potassium ions was confirmed based on the increase in gelation and melting temperatures in Example 2-3 compared to Example 2-1. The tensile strength of the dried film remained comparable to examples 2-1 and 2-2.

[0082] Example 2-4 illustrates the effect of replacing the maltodextrin of example 2-3 with modified starch (B790). Although the viscosity increased, the gelation and melting temperatures remained quite similar to example 2-3, in which maltodextrin was used. The strength of the poured film of example 2-4 was also almost equal to that of example 2-3. The strength of the dried film of example 2-4 was more than double compared to example 2-3. This undoubtedly means structural synergy between starch and kappa-2-carrageenan, if both substances are present with potassium cations (i.e. gelling ions of kappa-2-carrageenan). Potassium ions can be introduced by the direct addition of inorganic salts, organic salts or combinations thereof, or they may be in additional ingredients. The use of kappa-2-carrageenan containing process salt residues can promote the formation of desirable gel forming conditions that maximize the synergy of gel and starch structure. A homogeneous gel structure of kappa-2-carrageenan and starch was produced by pouring molten mass at a sufficiently high temperature to prevent premature gelation.

[0083] Additional recipes of the present invention are provided immediately below.

Table V: Kappa-2-carrageenan films

<td></td><td>Example 2-5</td><td>Example 2-6</td><td>Example 2-7</td>

<td>Ingredients, (g)</td><td></td><td></td><td></td>

<td>water</td><td> 834,7</td><td> 834,7</td><td> 825</td>

<td>CgnH</td><td> 61,4</td><td> 0</td><td> 0</td>

<td>CgnG</td><td> 0</td><td> 0</td><td> 90</td>

<td>CgnI</td><td> 0</td><td> 75,0</td><td> 0</td>

<td>calcium sulfate dihydrate</td><td> 1,7</td><td> 0</td><td> 0</td>

<td>potassium chloride</td><td> 0</td><td> 15,0</td><td> 0</td>

<td>starch B760</td><td> 0</td><td> 0</td><td> 225</td>

<td>M-100</td><td> 227,3</td><td> 227,3</td><td> 0</td>

<td>sorbitol SP</td><td> 275,4</td><td> 272,2</td><td> 272,2</td>

<td>glycerine</td><td> 91,9</td><td> 90,8</td><td> 90,8</td>

<td colspan="4"></td>

<td>temperature, ° C *</td><td> 82</td><td> 88</td><td> 75</td>

<td>viscosity, mPa s *</td><td> 6500</td><td> 16 150</td><td> 18 250</td>

<td>solids (estimated)</td><td> 39</td><td> 42</td><td> 40</td>

<td>Melting point, ° C</td><td> 74-77</td><td> 85</td><td> 62-65</td>

<td>gelation, ° C</td><td> 56</td><td> 60-65</td><td> 42</td>

<td>pH</td><td> 5,8</td><td> 6,9</td><td> 6,9</td>

<td colspan="4">in the form of poured foil</td>

<td>breaking load (g) at ~ 40%)</td><td> 338</td><td> 302</td><td> 117</td>

<td colspan="4">foil dried for 2 hours at 40 ° C</td>

<td>breaking load (g) (at -60%)</td><td> 766</td><td>not studied</td><td> 536</td>

<td>foil dried for 16 hours at 40 ° C</td><td></td><td></td><td></td>

<td>average film thickness, mm</td><td> -</td><td> 0,62</td><td> -</td>

<td>breaking load (g) at -80%</td><td> 3227</td><td> 4470</td><td> 6073</td>

<td colspan="4">* temperature and viscosity of the molten mass before pouring</td>

[0084] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

[0085] Example 2-5 was developed so that the content of cations was the same as in Example 1-1. Both samples show almost equal melting points of the gel. The higher molecular weight Cgn E (14 cP) in Example 1-1 provided the gel film with better structural support compared to Cgn H (6 cP) in Example 2-5, as indicated by the higher load required to break the dried film. The greater strength of the dried film of Example 2-7 indicates that the use of modified starch in combination with kappa-2-carrageenan with modified or reduced molecular weight gives the overall structure of the film and that complexation of kappa-2-carrageenan with starch occurs.

Example 3 [0086] Table VI details the composition and properties of films containing kappa-2-carrageenans mixed with alginates. KAHG is potassium alginate derived from Laminaria hyperborea seaweed, characterized by a high level of guluron (G) units. KAHG had a viscosity of 5 cP, as measured in a 1% aqueous solution at 25 ° C, and an ion content of 15.73% potassium, 0.63% sodium and 0.07% magnesium (no calcium). Protanal® BV4830 ester is propylene glycol alginate available from FMC BioPolymer (Philadelphia, Pennsylvania).

Table VI: Mixtures of kappa-2-carrageenan and alginate

<td></td><td>Example 3-1</td><td>Example 3-2</td>

<td>Ingredients</td><td></td><td></td>

<td>water</td><td> 55,6%</td><td> 55,6%</td>

<td>CgnG</td><td></td><td></td>

<td>CgnC</td><td> 2,7%</td><td> 3,6%</td>

<td>KAHG</td><td> 2,1%</td><td></td>

<td>BV4830</td><td> 1,2%</td><td> 2,4%</td>

<td>starch B760</td><td></td><td></td>

<td>M-100</td><td> 15,0%</td><td> 15,0%</td>

<td>sorbitol SP</td><td> 18,0%</td><td> 18,0%</td>

<td>glycerine</td><td> 6,0%</td><td> 6,0%</td>

<td>temperature, ° C *</td><td> 87</td><td> 84</td>

<td>viscosity, mPa s *</td><td> 4250</td><td> 1050</td>

<td>solids</td><td> 40</td><td> 37</td>

<td>Melting point, ° C</td><td> 77-78</td><td> 74-79</td>

<td>gelation, ° C</td><td> 54</td><td> 52</td>

<td>pH</td><td> 4,8</td><td> 5,5</td>

<td colspan="3">poured film (solids estimated 40%)</td>

<td>breaking load (g)</td><td> 142</td><td> 168</td>

<td colspan="3">dried film (solids 80% estimated)</td>

<td>average film thickness, (mm)</td><td> 0,62</td><td> 0,48</td>

<td>breaking load, (g)</td><td> 3409</td><td> 4004</td>

<td colspan="3">* temperature and viscosity of the molten mass before pouring</td>

[0087] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

[0088] In Example 3-1, potassium alginate provided potassium ions. Example 3-2 shows that propylene glycol alginate increases the strength of kappa-2-carrageenan and reduces process viscosity.

Example 4 [0089] Table VII describes a film made from blends of kappa-2-carrageenan and Edicol ULV 50, i.e. low viscosity guar gum, manufactured by Indian Gum Industries.

[0090] Cgn K was a kappa-2-carrageenan obtained as alkali-clarified extract from Gigartina skottsbergii, plants usually haploid (gametophytes). In addition, small amounts (less than 5% in total) of lambda- and tetacaragens from diploid plants (tetrasporophytes) were found. Cgn K had a low content of divalent and potassium cations, as seen in Table I.

[0091] Cgn L was a kappa-2-carrageenan obtained as an alkali, clarified extract from a mixture of Gigartina skottsbergii and Sarcothalia crispata, plants usually haploid (gametophytes). About 10-20% (total) of lambda- and theta-carrageenans from diploid plants (tetrasporophytes) were also found. The properties of Cgn K and L are as below.

Table VII: Properties of kappa-2-carrageenan

<td></td><td>Cgn K</td><td>Cgn L.</td>

<td>cation exchange</td><td>Yes</td><td>no</td>

<td>Mg,%</td><td> 0,05</td><td> 0,05</td>

<td>Ca,%</td><td> 0,15</td><td> 0,45</td>

<td>K%</td><td> 0,67</td><td> 13,40</td>

<td>Na,%</td><td> 7,40</td><td> 0,90</td>

<td>viscosity, mPs</td><td> 98</td><td>not studied</td>

<td>pH</td><td> 10,1</td><td>not studied</td>

<td>water gel, 2%</td><td></td><td></td>

<td>breaking load (g)</td><td> 0</td><td>not studied</td>

<td>water gel (KCl), 2%</td><td></td><td></td>

<td>breaking load (g)</td><td> 38</td><td>not studied</td>

<td>water gel (KC1 + CaCbk 2%</td><td></td><td></td>

<td>breaking load (g)</td><td> 181</td><td>not studied</td>

[0092] Table VIII shows the composition of the stocks and the properties of the films obtained using low viscosity guar gum in combination with kappa-2-carrageenans.

Table VIII: Composition of stocks and properties of films containing guar gum and kappa-2caragens

<td></td><td>Example 4-1</td><td>Example 4-2</td><td>Example 4-3</td><td>Example 4-4</td>

<td>Ingredients, g</td><td></td><td></td><td></td><td></td>

<td>water</td><td> 836,3</td><td> 836,3</td><td> 836,3</td><td> 836,3</td>

<td>CgnL</td><td> 40,5</td><td> 20,3</td><td> 0,0</td><td> 0,0</td>

<td>CgnK</td><td> 0,0</td><td> 20,3</td><td> 40,5</td><td> 40,5</td>

<td>ULV 50 GUAR</td><td> 49,5</td><td> 49,5</td><td> 49,5</td><td> 49,5</td>

<td>starch B760</td><td> 220,8</td><td> 220,8</td><td> 220,8</td><td> 220,8</td>

<td>potassium chloride</td><td> 0,0</td><td> 0,0</td><td> 4,5</td><td> 4,5</td>

<td>sorbitol SP</td><td> 264,4</td><td> 264,4</td><td> 264,4</td><td> 264,4</td>

<td>glycerine</td><td> 88,2</td><td> 88,2</td><td> 88,2</td><td> 88,2</td>

<td>total weight (g)</td><td> 1500,0</td><td> 1500,0</td><td> 1500,0</td><td> 1500,0</td>

<td>temperature, ° C *</td><td> 90</td><td> 90</td><td> 87</td><td> 95</td>

<td>viscosity, mPa s *</td><td> &gt; 50000</td><td> &gt; 50000</td><td> &gt; 50000</td><td> &gt; 50000</td>

<td colspan="5">after pouring</td>

<td>gelation, ° C</td><td> 68-69</td><td> 69</td><td> 50</td><td> 54-65</td>

<td>Melting point, ° C</td><td> 85-87</td><td> 86-88</td><td> 67-68</td><td> 76-83</td>

<td>pH</td><td> 5,8</td><td> 5,9</td><td> 5,2</td><td> 5,2</td>

<td colspan="5">poured foil</td>

<td>solids (estimated)</td><td> 45%</td><td> 42%</td><td> 40,2%</td><td> 45%</td>

<td>breaking load (g)</td><td> 239</td><td> 349</td><td> 130</td><td> 330</td>

<td colspan="5">dried foil (2 hours, 40 ° C)</td>

<td>solids (estimated)</td><td> 60%</td><td> 60%</td><td> 63%</td><td> 66%</td>

<td>breaking load (g)</td><td> 953</td><td> 2189</td><td> 1194</td><td> 1631</td>

<td colspan="5">dried film (16 hours, 40 ° C)</td>

<td>solids (estimated)</td><td> 87%</td><td> 75%</td><td> 84%</td><td> 84%</td>

<td>breaking load (g)</td><td> 7476</td><td> 6901</td><td> 6276</td><td> 8733</td>

<td colspan="5">* temperature and viscosity of the molten mass before pouring</td>

[0093] All of the above compositions of the present invention gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

Example 5 [0094] The following examples illustrate exemplary films made using the fluid mixer 10 of Fig. 3. In these examples, part A and part B were pumped from separate storage tanks, at ambient temperature, as two separate streams 4, 6 to two different inlet ports 42, 44 of the above-mentioned liquid mixer 10 and injected through the steam nozzle. Both of these streams 4, 6 were in contact with each other at the point of contact with steam 2 in mixing zone 52 of the fluid mixer 10. Separate solutions (part A and part B) were easy to pump into the fluid mixer 10, and mixed with steam 2, which the mixing chambers were introduced at a pressure of 120 psi (about 827 kPa). The resulting molten mass or suspension mixture 8 flowed from the outlet port 56 of the fluid mixer 10. The mixture 8 was then poured and spread over a smooth surface to form a homogeneous film 9.

[0095] To measure the viscosity of the suspension mixture 8, a sample of approximately 500 ml was taken from outlet port 56 and poured into a jar. The viscosity and pH of this sample was determined at 95 ° C. A Brookfield LVF viscometer was used to determine the viscosity. Readings from the disk, which were converted into dynamic viscosity expressed in centipoise (cP), were possible by an appropriate combination of the spindle and its rotational speed.

[0096] To measure film strength and solids content, molten mass 8 was taken from outlet port 56 and spread using a rod applicator in which the gap was set to give a clearance of 3 mm over a stainless steel plate. Then the formed ("fresh") films 9 were removed, the sections of which were dried by placing them in a 40 ° C forced air oven. Breaking load, both for fresh and dried film strips, was determined using the TA-108S film strength testing device. The percentage of solids was determined by the weight method based on the difference between the initial weight of fresh film and the final weight of dried films.

[0097] To determine the gelation temperature, a sample of molten mass 8 was taken from the outlet connector 56 of the mixer 10 and placed in a tube so that half of it was empty. A glass thermometer was added to molten mass 8 and it was cooled at room temperature. After each decrease in the sample temperature by one degree, the thermometer was removed from the mass 8. If a slight, temporary depression was noticed on the surface of the mixture, this temperature was recorded. The thermometer was reinserted into the sample, which was further cooled. After each cooling of the sample by one degree, the thermometer was removed from mass 8 and introduced again - until a permanent, i.e. non-filling, recess in the surface was formed. The temperature at which this permanent depression formed was recorded. The gelation temperatures reported are the range between the two temperatures noted.

Table IX: Mixtures containing kappa-2-carrageenan

<td></td><td>Example 5-1</td><td>Example 5-2</td><td>Example 5-3</td>

<td>Part A (%)</td><td></td><td></td><td></td>

<td>kappa-2-carrageenan A</td><td> 7,0</td><td> 8,4</td><td> 8,9</td>

<td>glycerine</td><td> 26,5</td><td> 31,8</td><td> 33,5</td>

<td></td><td></td><td></td><td></td>

<td>Hello B (%)</td><td></td><td></td><td></td>

<td>starch</td><td> 16,4</td><td> 19,7</td><td> 20,7</td>

<td>water</td><td> 50,0</td><td> 40,0</td><td> 36,9</td>

<td></td><td></td><td></td><td></td>

<td>mixing chamber temperature, (° C)</td><td> 107</td><td> 107</td><td> 108</td>

<td>outlet temperature, (° C)</td><td> 101</td><td> 102</td><td> 102</td>

<td>viscosity cP (95 ° C)</td><td> 7300</td><td> 5200</td><td> 48000</td>

<td>pH</td><td> 7,3</td><td>not studied</td><td> 8</td>

<td>% solids</td><td> 53</td><td> 54</td><td> 65</td>

<td>gelation temperature, ° C</td><td> 46-50</td><td> 43-47</td><td> 53-60</td>

<td>wet film strength (g)</td><td> 267</td><td> 214</td><td> 983</td>

<td>dry film strength (g)</td><td> 2958</td><td> 6798</td><td> 4594</td>

<td>average film thickness, (mm) (% solids)</td><td></td><td></td><td> 1,3 (74%) 1,7 (59%)</td>

[0098] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

Table X: Mixtures containing kappa-2-carrageenan and PGA

<td></td><td>Example 5-4</td><td>Example 5-5</td><td>Example 5-6</td><td>Example 5-7</td>

<td>Part A (%)</td><td></td><td></td><td></td><td></td>

<td>kappa-2-carrageenan A</td><td> 2,7</td><td> 3,2</td><td> 3,2</td><td> 4,0</td>

<td>PGA</td><td> 3,3</td><td> 3,9</td><td> 3,9</td><td> 4,9</td>

<td>glycerine</td><td> 22,4</td><td> 26,5</td><td> 26,5</td><td> 33,5</td>

<td></td><td></td><td></td><td></td><td></td>

<td>Hello B (%)</td><td></td><td></td><td></td><td></td>

<td>KOH</td><td> 0,0</td><td> 0,0</td><td> 0,1</td><td> 0,0</td>

<td>K₂WHAT₃</td><td> 0,0</td><td> 0,0</td><td> 0,0</td><td> 0,3</td>

<td>starch</td><td> 13,9</td><td> 16,4</td><td> 16,4</td><td> 20,7</td>

<td>water</td><td> 57,8</td><td> 50,0</td><td> 49,9</td><td> 36,6</td>

<td></td><td></td><td></td><td></td><td></td>

<td>mixing chamber temperature (° C)</td><td> 108</td><td> 107</td><td> 108</td><td> 107</td>

<td>outlet temperature (° C)</td><td> 102</td><td> 102</td><td> 102</td><td> 101</td>

<td>viscosity cP (95 ° C)</td><td> 5500</td><td> 4650</td><td> 2200</td><td> 12 400</td>

<td>pH</td><td> 4,1</td><td> 4,2</td><td> 8,7</td><td> 6,3</td>

<td>% solids</td><td> 48</td><td> 50</td><td>not studied</td><td> 58</td>

<td>gelation temperature, (° C)</td><td> 35-40</td><td>not studied</td><td>not studied</td><td> 58-66</td>

<td>wet film strength (g)</td><td> 60</td><td> 117</td><td>not studied</td><td> 337</td>

<td>dry film strength (g)</td><td> 2408</td><td> 3069</td><td> 4335</td><td> 4561</td>

<td>average film thickness (mm) (% solids)</td><td></td><td></td><td></td><td> 1,2 (91%) 1,1 (57%)</td>

[0099] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others.

Table XI: Mixtures containing kappa-2-carrageenan and low-viscosity guar gum

<td></td><td>Example 5-8</td><td>Example 5-9</td>

<td>Part A (%)</td><td></td><td></td>

<td>kappa-2-carrageenan B</td><td> 4,0</td><td> 4,2</td>

<td>guar ULV</td><td> 4,9</td><td> 5,1</td>

<td>glycerine</td><td> 33,5</td><td> 27,0</td>

<td>sorbitol</td><td> 0,0</td><td> 8,1</td>

<td></td><td></td><td></td>

<td>Hello B (%)</td><td></td><td></td>

<td>starch</td><td> 20,7</td><td> 21,8</td>

<td>water</td><td></td><td></td>

<td></td><td></td><td></td>

<td>mixing chamber temperature, (° C)</td><td> 108</td><td> 108</td>

<td>outlet temperature, (° C)</td><td> 102</td><td> 102</td>

<td>viscosity, cP (95 ° C)</td><td> 7800</td><td> 69 000</td>

<td>PH</td><td> 5,6</td><td> 5,5</td>

<td>% solids</td><td> 57</td><td> 55</td>

<td>gelation temperature (° C)</td><td> &gt; 100</td><td> &gt; 100</td>

<td>wet film strength (g)</td><td> 3402</td><td> 921</td>

<td>dry film strength (g)</td><td> 6587</td><td> 9234</td>

[0100] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others. [0101] The following Tables XII and XIII describe the ingredients used in this example. Table XII: Descriptions of ingredients

<td>Name</td><td>trade name</td><td>Supplier</td><td>Description</td>

<td>glycol alginate</td><td>Protanal BV 4830</td><td>FMC Corporation</td><td></td>

<td>propylene (PGA)</td><td></td><td></td><td></td>

<td>low viscosity guar gum (LV guar)</td><td>Edicol ULV 50</td><td>Indian Gum Industries Co., Ltd.</td><td></td>

<td>glycerine</td><td></td><td>Callahan Chemical</td><td> 99,70%</td>

<td>sorbitol</td><td>Sorbo</td><td>SPI Polyols</td><td>70% sorbitol solution, compliant with the American Pharmacopoeia and the Substance Code chem. in food</td>

<td>starch</td><td>Pure-Cote B790</td><td>Grain Processing Corporation</td><td></td>

Table XIII: Description of carrageenans

<td>Name</td><td>Description</td><td>Supplier</td>

<td>kappa-2caragen A.</td><td>Treated with alkali and clarified extract, low in divalent cations, from a mixture of Gigartina skottsbergii and Sarcothalia crispata, mainly haploid plants (gametophytes), such an extract is known in the industry as "kappa-2-carrageenan". It contains about 10-20% (total) lambda- and theta-carrageenans from diploid plants (tetrasporophytes). Defined as a natural, statistical block copolymer of kappa and iota-carrageenans in a ratio of about 1.0: 1 to 3.0: 1, respectively, it has significantly different properties than the mixed natural polymers of kappa and iota-carrageenan in the same ratio.</td><td>FMC Corporation</td>

<td>kappa-2karagen B.</td><td>Treated with alkali and clarified extract with a low content of divalent cations from Gigartina skottsbergii, essentially haploid plants (gametophytes), such an extract is known in the industry as "kappa-2-carrageenan". It also contains small amounts (less than 5% in total) of lambda and theta-carrageenans from diploid plants (tetrasporophytes). Defined as a natural, statistical block copolymer of kappa and iota-carrageenans in a ratio of about 1.0: 1 to 3.0: 1, respectively, and has significantly different properties than mixed natural polymers of kappa and iota-carrageenan in the same ratio .</td><td>FMC Corporation</td>

[0102] As discussed and demonstrated above, the films obtained in accordance with the present invention can be used in standard capsule making devices previously used to produce gelatin capsules. The hydrocolloid films produced according to the present invention generate less waste and provide easier processing compared to gelatin-based films.

Example 6 [0103] Kappa-2-carrageenans were obtained as alkali-treated clarified extracts from Gigartina skottsbergii and Sarcothalia crispata, using mainly haploid plants (gametophytes), respectively. The total lambda- and theta-carrageenan content of diploid plants (tetrasporophytes) ranged from about 0% to 5% for Gigartina skottsbergii and from about 5% to 10% for Sarcothalia crispata. The extracts were isolated, followed by ion exchange to obtain kappa-2-carrageenans with a low content of divalent cations. The properties of kappa-2-carrageenans are shown in Table XIV; they are considered to fall within the scope of the invention.

Table XIV: Properties of kappa-2-carrageenans with sodium and potassium

<td></td><td>Cgn Na K2-S</td><td>Cgn K K2-S</td><td>Cgn Na K2-N</td><td>Cgn Κ K2-N</td>

<td>Source (seaweed)</td><td>Gigartina skottsbergii</td><td>Gigartina skottsbergii</td><td>Sarcothalia crispata</td><td>Sarcothalia crispata</td>

<td>Mg,%</td><td> 0,00</td><td> 0,12</td><td> 0,03</td><td> 0,12</td>

<td>Ca,%</td><td> 0,04</td><td> 0,34</td><td> 0,11</td><td> 0,43</td>

<td>K%</td><td> 1,24</td><td> 9,27</td><td> 1,35</td><td> 8,63</td>

<td>Na,%</td><td> 6,53</td><td> 0,68</td><td> 7,23</td><td> 1,34</td>

<td>viscosity, mPs</td><td> 45,5</td><td> 39,5</td><td> 62,5</td><td> 31,5</td>

<td>pH</td><td> 7,46</td><td> 8,51</td><td> 7,1</td><td> 7,91</td>

<td>Water gel, 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td>beginning</td><td> 38</td><td> 17</td><td> 102</td>

<td>penetration (cm)</td><td> 7,46</td><td> 6,9</td><td> 21</td><td> 12,1</td>

<td>Water gel (KC1), 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td> 10</td><td> 134</td><td> 30</td><td> 179</td>

<td>penetration (cm)</td><td> 5,7</td><td> 1,9</td><td> 5,0</td><td> 2,7</td>

<td>Water gel (KC1 + CaC12), 2%</td><td></td><td></td><td></td><td></td>

<td>breaking load (g)</td><td> 112</td><td> 279</td><td> 114</td><td> 263</td>

<td>penetration (cm)</td><td> 2,1</td><td> 2,7</td><td> 2,7</td><td> 2,0</td>

<td colspan="5">K2 = kappa-2-carrageenan</td>

[0104] The composition of the kappa-2-carrageenan feeds and the properties of the corresponding films are shown in Table XV. These films were formed by a method using a distribution chamber. The input materials contained a 50/50 mix of kappa-2-carrageenans from Gigartina skottsbergii and Sarcothalia crispata and they differed in potassium cations.

All of the following recipes are considered to fall within the scope of the present invention, although some may be more favorable than others for a given application.

Table XV: Kappa-2-carrageenan films from different seaweed and with different cation content

<td></td><td>Example 1</td><td>Example 2</td><td>Example 3</td><td>Example 4</td>

<td>Ingredients (g)</td><td></td><td></td><td></td><td></td>

<td>On K2-S *</td><td> 162,6</td><td> 162,6</td><td> 195,1</td><td> 0,0</td>

<td>On K2S-N *</td><td> 162,6</td><td> 0,0</td><td> 195,1</td><td> 0,0</td>

<td>K K2S-S *</td><td> 0,0</td><td> 0,0</td><td> 0,0</td><td> 162,6</td>

<td>K K2-N *</td><td> 0,0</td><td> 162,6</td><td> 0,0</td><td> 162,6</td>

<td>water</td><td> 1851,5</td><td> 1851,5</td><td> 1851,5</td><td> 1851,5</td>

<td>starch B790</td><td> 858,5</td><td> 858,5</td><td> 858,5</td><td> 858,5</td>

<td>glycerine</td><td> 1300,8</td><td> 1300,8</td><td> 1300,8</td><td> 1300,8</td>

<td>As cast foil</td><td>Example 1</td><td>Example 2</td><td>Example 3</td><td>Example 4</td>

<td>gelation, ° C</td><td> 35-40</td><td> 63</td><td> 50</td><td> 58</td>

<td>Melting point, ° C</td><td> 58-60</td><td> 83-85</td><td> 69</td><td> 93-95</td>

<td>pH</td><td> 5,3</td><td> 5,6</td><td> 6,6</td><td> 5,6</td>

<td>In the form of a cast film</td><td></td><td></td><td></td><td></td>

<td>solids (estimated)</td><td> 57,3%</td><td> 57,3%</td><td> 57,3%</td><td> 57,3%</td>

<td>breaking load (g)</td><td> 214,3</td><td> 610,5</td><td> 459,1</td><td> 901,4</td>

<td>penetration (cm)</td><td> 2,0</td><td> 1,6</td><td> 2,1</td><td> 1,6</td>

<td>In the form of dried film (16 hours, 40 ° C)</td><td></td><td></td><td></td><td></td>

<td>solids (estimated)</td><td> 95</td><td> 91</td><td> 86</td><td> 93</td>

<td>breaking load (g)</td><td> 5132</td><td> 6902</td><td> 8914</td><td> 4517</td>

<td>penetration (cm)</td><td> 2,3</td><td> 1,8</td><td> 1,8</td><td> 1,6</td>

<td colspan="5">* kappa-2-carrageenan</td>

[0105] All of the above compositions gave sufficient dry film strength to produce soft capsules, although some were more durable than others. The kappa-2-carrageenan sodium form (Examples 1 and 3) gave greater flexibility, while the completely potassium form (Example 4) provided stiffer films, but still useful. The processing of the feed containing the potassium form of kappa-2-carrageenan was also difficult because the gelation of the mixture began when it was transported from the Ross mixer to the film making machine. The films obtained in Example 4 had lower strength, most likely due to premature gelation during transport and / or the film production process. Very efficient temperature control is necessary if it is required to increase the film's strength to the maximum and to prevent the melted mass from rapidly moving into a rubber-like state and then into a glassy state (glass transition temperature). In the case of films using kappa-2-carrageenan with "mixed cations" (example 2), it provides the properties of molten mass and film poured indirectly, relative to films containing kappa-2-carrageenan only with sodium cations or only potassium cations, with elevated gelation temperature and less elasticity (as indicated by the penetration value) compared to kappa-2-carrageenan containing only sodium cations.

Example 7

Example of a soft capsule [0106] Soft gel capsules (oval, size 7.5) containing mineral oil (recipe A below) were prepared using a Technophar SGM-1010 soft capsule making machine with matrices of 7.25 inches in diameter and 4 inches in diameter. Preparation of the molten mass used to make the capsule shell was as follows.

An 11.35 pound portion of kappa-2-carrageenan (present in example 5 as kappa-2-carrageenan A) was added to a 33.89 pound glycerin feed in a Ross DS40 vacuum jacketed mixer and dispersed at maximum speed for 5 minutes after and an additional 11.35 pounds of kappa-2-carrageenan (present in example 5 as kappa-2-carrageenan A) was added to the mixture and dispersed for a further 5 minutes. Then 50 pounds of Pure-Cote B790 modified starch pre-mixed with 94.1 pounds of deionized water was introduced into the mixer. The mixer cover was closed and a 26 inch vacuum was connected to remove air. The contents were mixed for 30 minutes using a planetary mixer at maximum speed and a dispersion device at 1/3 of the maximum speed. The vacuum was blocked and the contents of the apparatus were then mixed while heating to 90 ° C with low pressure steam (&lt;10 psig) fed into the jacket of the mixer. After reaching a temperature of 90 ° C, the rotational speed of the dispersion was gradually increased to 2/3 of the maximum value, while maintaining the temperature of the molten mass at least 90 ° C for 45 minutes. The molten mass was dosed, by means of a pressure plate forcing the flow of molten mass from the Ross mixer as needed, through a flexible temperature-controlled hose, electrically heated (~ 125 ° C), into a closed distribution chamber. The poured films, shaped by this chamber, were continuous and even. The films were transferred by means of rollers (rolls) to encapsulation matrices in which capsules were formed, filled with mineral oil and heat-sealed. The sealing temperature of the capsules was 62 ° C and the pressure was about 2 bars. The sealing quality improved as the web thickness decreased from 0.28 inches to 0.16 inches. The capsules were tunnel dried for 72 hours at 80 ° F, 19% relative humidity. The seal tightness of the capsule after drying remained adequate. Cast films produced from this formulation with the above recipe were dark amber and opaque, with a weak smell of seaweed. The breaking load of this film (0.3 mm thick) was 310 g with a solids content of 58%. After drying overnight at 40 ° C and 40% relative humidity, the strength of this film (about 80% solids) was 3309 G (see formulation A in the table below).

[0107] Additional soft capsules (formulation B below) encapsulated with mineral oil were prepared according to the above method and equipment using a second formulation containing 39.7 pounds of sorbitol SP, 59.5 pounds of glycerin, 19.6 pounds of kappa-2-carrageenan ion exchanged for sodium cations (a mixture of carrageenans J and I, as above, in a ratio of 50:50), 44.6 pounds of Pure-Cote B760 starch and 92.6 pounds of water. Sorbitol SP was added to the pre-mixed starch and water. The films made from this batch were odorless, transparent and moderately colored. The film thickness after pouring was 0.6 mm, and the breaking strength 263 g at 55% solids concentration, while after drying overnight at 40 ° C and 40% relative humidity (which increased the solids concentration to about 80%) it had 0.7 mm thick and 6463 g breaking strength. The film after pouring (not dried) was more elastic and stretched when guided on rollers to encapsulation matrices. Capsules (with mineral oil) were formed at a sealing temperature of 42 ° C and a pressure of 0.5 bar. Mineral oil was encapsulated.

[0108] Capsules were evaluated for weight, film thickness of each half of the capsule, and breaking strength. This strength was measured by squeezing the capsule until it bursts. The speed of the compression tester was 1 mm / s. Ten capsules were tested under all conditions. The shell strength is the capsule's breaking strength when the joint is horizontal. The joint strength was measured for 10 capsules at the vertical position of the joint. The results are given in Table XVI. Both kappa-2-carrageenan films were flexible, as indicated by the distance at break, and allowed for a strong capsule joint, as indicated by almost the same tear strength of the capsule for the envelope and joint, and the capsule did not break at the joint, but on connector tip (outside the pressure point).

Table XVI: Capsule properties

<td>Recipe capsules</td><td>Mass capsule mg</td><td>Foil weight / weight fill mg</td><td>Foil 1 / foil 2 thickness, mm</td><td>Distance at shell break, mm</td><td>Strength casings, newtons</td><td>Distance at connector breakage, mm</td><td>Strength connectors, newtons</td>

<td>Recipe A</td><td> 471</td><td> 151/320</td><td> 357/312</td><td> 6,3</td><td> 206</td><td> 6,3</td><td> 210</td>

<td>Recipe B</td><td> 499</td><td> 187/312</td><td> 420/370</td><td> 5,3</td><td> 124</td><td> 5,1</td><td> 105</td>

Example 8 [0109] Kappa-2-carrageenan was prepared from Sarcothalia crispata seaweed containing in the final composition approximately 74% unmodified kappa-2-carrageenan and 26% lambda-carrageenan. As a 1.5% aqueous solution of kappa-2-carrageenan at 75 ° C it had a viscosity of 340 cP and a pH of 9.4. The ion content was approximately: 4.4% potassium, 4.0% sodium, 0.2% calcium and 0.4% magnesium. A composition was prepared by adding 2% kappa-2-carrageenan to a mixture of 20% glycerin and 78% deionized water, after which it was heated while stirring to 85 ° C, which temperature was maintained, followed by stirring, for 15 minutes. The lost water was made up with deionized water at 85 ° C. The resulting mixture was poured into a Petri dish and then dried overnight at 45 ° C to obtain a film with a solids content of approximately 80%. The dried film's breaking strength was 469 grams and the penetration was 3.3 cm.

Example 9 [0110] The following procedure was used to obtain a sample containing 2.25% kappa-2-carrageenan with different molecular weight (as indicated by viscosity, measured at 75 ° C in an aqueous solution with a solids concentration of 1.5%), 105 grams of water and 147 grams of corn syrup were mixed in a beaker. A dry mix of kappa-2-carrageenan, granulated sugar and salt (as in Table XVII) was added to the liquid and heated to 95 ° C with stirring. The hot liquid was poured into 2 gelling plates and into 2 tubes (up to half the volume). The gel plates and one test tube (tilted to obtain a gel surface at 45 degrees for use in measuring melting point) were placed for one hour in a 10 ° C water bath. A second tube was used to measure gelation temperature. The solids content after pouring was approximately 62%. Gel and melting temperatures of samples 1b, 2b and 3b, which contained added potassium and calcium cations, were above 50 ° C and increased very slightly with the increase in molecular weight. Gel and melting temperatures of Ia, 2a and 3a samples that contained ion exchanged kappa2-carrageenans were in all cases less than 50 ° C. Gelation and melting temperatures decreased as the molecular weight decreased (compared on the basis of viscosity). In particular, sample la, which contained kappa-2-carrageenan with a viscosity of 9 mPa s, gave a gel film with a very low gelation temperature of 25 ° C and a melting point of 36 ° C.

Table XVII: Composition of charges and properties of films containing kappa-2-carrageenans

<td></td><td>la</td><td>2a</td><td>3a</td><td>lb</td><td>2b</td><td>3b</td>

<td>Ingredient (g)</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>K2 (9 mPas) Cgn H</td><td> 7,88</td><td> 0</td><td> 0</td><td> 7,88</td><td> 0</td><td> 0</td>

<td>K2 (20 mPa-s) Cgn I</td><td> 0</td><td> 7,88</td><td> 0</td><td> 0</td><td> 7,88</td><td> 0</td>

<td>K2 (41 mPa-s) CgnJ</td><td> 0</td><td> 0</td><td> 7,88</td><td> 0</td><td> 0</td><td> 7,88</td>

<td>sugar</td><td> 90,13</td><td> 90,13</td><td> 90,13</td><td> 88,78</td><td> 88,78</td><td> 88,78</td>

<td>CaCl₂</td><td> 0</td><td> 0</td><td> 0,0</td><td> 0,58</td><td> 0,58</td><td> 0,58</td>

<td>KC1</td><td> 0</td><td> 0</td><td> 0,0</td><td> 0,76</td><td> 0,76</td><td> 0,76</td>

<td>As poured foil</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>breaking load, (g)</td><td>not broken</td><td>not broken</td><td>not broken</td><td> 819</td><td> 964</td><td> 1178</td>

<td>penetration, cm</td><td></td><td></td><td></td><td> 5,0</td><td> 13,0</td><td> 7,5</td>

<td>Temp, melting, ° C</td><td> 36</td><td> 39,5</td><td> 42</td><td> 75</td><td> 76-77</td><td> 77</td>

<td>Temp, gelation, ° C</td><td> 25</td><td> 35,5</td><td> 34-36</td><td> 57</td><td> 58,5-60</td><td> 58-59</td>

<td colspan="7">K2 = kappa-2-carrageenan</td>