Film formation delayed / enteric formulations for hard shell capsules, films and coatings

Abstract

The present invention relates to aqueous film-forming compositions suitable for use in capsule films, capsule shells, as well as methods for producing such capsule films, capsule shells and uses thereof.

Description

Technical Field

[0001] The present invention relates to an aqueous film-forming composition suitable for capsule films and capsule shells, as well as a method for producing such capsule films and capsule shells and their use. Background Art

[0002] Capsules are widely used to administer drugs and nutrients to humans and animals. Capsules also have different uses, such as acting as a reservoir for plant fertilizers to facilitate application, a reservoir for colorants, a reservoir for food materials or food supplements, and a reservoir for cosmetic ingredients. Alginate is a convenient material for the capsule membrane portion because it can be formed during the process of preparing the capsule.

[0003] Alginates are high molecular weight polysaccharides extracted from various species of brown seaweed with dilute alkali. They are hydrophilic colloidal carbohydrates that are water-soluble biopolymers with colloidal properties when hydrated. In terms of chemical structure, they are linear copolymers of 1,4-linked β-D-mannuronic acid and β-L-guluronic acid, which consist of three different polymer segments: polymannuronic acid segments (M blocks), polyguluronic acid segments (G blocks), and alternating mannuronic acid units and guluronic acid units (MG blocks). A wide range of these polymers are available in alginic acid, various salt forms, propylene glycol esters varying in molecular weight, particle size, M / G ratio and viscosity. Alginates have attracted attention as potential biopolymer film or coating components because of their unique colloidal properties, including thickening, stabilization, suspension, film formation, gel production and emulsion stabilization. Alginic acid and its derivatives have been used in the food processing industry, the biotechnology industry for the production of beads for immobilization of cells or enzymes, the pharmaceutical industry for tablet disintegration, controlled release, encapsulation, as films and coatings, lubricants, to prevent gastric reflux, gelling and as thickeners to stabilize emulsions and suspensions.

[0004] Sodium alginate is a natural, biocompatible, biodegradable and hydrophilic polymer suitable for embedding bioactive ingredients, such as drugs. Sodium alginate is easily hydrated in water, the solution is stable in the pH range of 4-10 and forms a strong, transparent film upon drying.

[0005] US 4365060 discloses enteric capsules, which are said to have excellent enteric behavior. These capsules are prepared by mixed esters of alkyl, hydroxyalkyl or hydroxyalkyl alkyl cellulose esterified with succinic anhydride and aliphatic monocarboxylic anhydride. The US patent discloses that the cellulose derivative can be formed into capsules not only by conventional impregnation methods but also by plastic deformation under pressure (such as compression molding, vacuum forming, mold matching molding, etc.) at elevated temperatures. The US patent points out that these enteric capsules have excellent flexibility even without adding plasticizer or adding a very small amount of plasticizer. Unfortunately, the impregnation method requires the use of organic solvents to dissolve the mixed esters of alkyl, hydroxyalkyl or hydroxyalkyl alkyl cellulose. It is usually not desirable to use organic solvents for medicine or nutrition purposes. In addition, the processing of organic solvents increases the complexity of the process for producing capsules. It is also usually not desirable to form capsules by plastic deformation, because the heat required for thermoforming causes significant thermal stress and thermal degradation and the mold required for thermoforming process is quite complicated and expensive.

[0006] US 9433585 describes a composition for making enteric soft capsules comprising gelatin, methacrylic copolymers, one or more plasticizers, an alkaline aqueous solvent, and optionally other ingredients such as colorants and flavorings. Capsules made from such a composition can be used to deliver acid-sensitive dosage forms to the lower digestive tract or provide delayed release of active pharmaceutical ingredients.

[0007] US2012 / 0161364 describes an aqueous composition for enteric hard capsules, a method for preparing enteric hard capsules, and an enteric hard capsule prepared using the method. WO 2013 / 164121 describes an aqueous composition comprising a hydroxypropylmethylcellulose acetate succinate (HPMCAS) polymer dispersed in water, wherein the dispersed polymer is partially neutralized with at least one alkaline material. This disclosure also relates to a composition for use in a method for manufacturing a capsule shell imparted with bulk enteric properties.

[0008] However, the enteric polymers used in the above prior art are not confirmed as Generally Recognized As Safe (GRAS) for food and nutritional applications. Considering the growing demand for encapsulating probiotics and other actives preferably delivered in the intestine, there is still a need for GRAS capsule materials and subsequent capsule films suitable for delayed release and / or enteric use. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 . Rheology of the formulations of the invention those listed in Tables 1 and 2.

[0010] Figure 2The membrane puncture strengths of the formulations of the present invention sufficient to form capsules are those listed in Tables 1, 2 and 3.

[0011] Figure 3 Examples of film appearance of films made from the formulations of Table 1, Table 2 and Table 3 after 2 hours in dissolution medium at pH 1.2. Summary of the invention

[0012] It is an object of embodiments of the present invention to provide an aqueous film-forming composition suitable for an improved capsule coating, film or capsule shell.

[0013] The present invention in a broad aspect relates to aqueous film-forming compositions suitable for delayed or enteric release of pharmaceutically or nutritionally active ingredients.

[0014] Thus, in a first aspect, the present invention relates to an aqueous film-forming composition comprising: a) an alginate having a viscosity in the range of about 2 to about 200 mPaS (1 mPaS equals 1 centipoise, also referred to as cp, cps or cPs) measured as a 1 wt% solution in water at 20°C; and b) a film-forming polymer having a viscosity in the range of about 2 to about 20 mPaS measured as a 2 wt% solution in water at 20°C.

[0015] In a second aspect, the present invention relates to the use of a composition according to the present invention for encapsulating a medicament, a nutritional supplement or a food supplement or a combination thereof.

[0016] In a third aspect, the present invention relates to a capsule film made from the composition according to the present invention.

[0017] In another aspect, the present invention is directed to a capsule shell comprising: a) an alginate having a viscosity in the range of about 2 to about 200 mPaS measured as a 1 wt % solution in water at 20°C; and b) a film-forming polymer having a viscosity in the range of about 2 to about 20 mPaS measured as a 2 wt % solution in water at 20°C.

[0018] In another aspect, the present invention relates to a capsule comprising a capsule shell prepared from the composition according to the present invention.

[0019] In another aspect, the present invention relates to a method for producing a capsule film, a capsule shell or a capsule, the method comprising the steps of providing an aqueous composition according to the present invention, preheating a moulding pin to a temperature of ±5°C of the maximum viscosity point of the aqueous composition above the gelling temperature, dipping the preheated moulding pin into the aqueous composition at a temperature below the gelling temperature, forming a film on the moulding pins by removing the moulding pins from the composition, and drying the film on the moulding pins at a temperature above the gelling temperature. DETAILED DESCRIPTION

[0020] As detailed above, the present invention relates to an aqueous film-forming composition comprising: a) an alginate having a viscosity in the range of about 2 to about 200 mPaS measured as a 1 wt % solution in water at 20°C; and b) a film-forming polymer having a viscosity in the range of about 2 to about 20 mPaS measured as a 2 wt % solution in water at 20°C.

[0021] In some embodiments, the alginate is selected from the group consisting of sodium alginate, potassium alginate, and other monovalent alginates; and mixtures thereof.

[0022] In some embodiments, wherein the alginate is sodium alginate.

[0023] In some embodiments, the alginate has a viscosity in the range of about 2 to about 100 mPaS, more preferably in the range of about 2 to about 30 mPaS, measured as a 1 wt % solution in water at 20°C.

[0024] In some embodiments, the film-forming polymer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC) and methyl cellulose (MC), hydroxypropyl cellulose (HPC); and mixtures thereof.

[0025] In some embodiments, the film-forming polymer has a viscosity in the range of about 3 to about 15 mPaS, more preferably in the range of about 3 to about 7 mPaS, measured as a 2 wt % solution in water at 20°C.

[0026] In some embodiments, the viscosity is measured using a Brookfield RV Viscometer using a Brookfield No. 2 spindle.

[0027] In some embodiments, the film-forming polymer is selected from the group consisting of: Hydroxypropyl methylcellulose 2910 (7%-12% HP, 28%-30% methoxy), Hydroxypropyl methylcellulose 2906 (4%-7.5% HP, 27%-30% methoxy), Hydroxypropyl methylcellulose 2208 (4%-12% HP, 19%-24% methoxy), Hydroxypropyl methylcellulose 1828 (23%-32% HP, 16.5%-20% methoxy), methylcellulose; and mixtures thereof.

[0028] In some embodiments, the composition according to the present invention further comprises a plasticizer.

[0029] In some embodiments, the plasticizer is selected from the group consisting of: a polyol, such as a sugar alcohol, such as propylene glycol, ethylene glycol, sorbitol, mannitol, erythritol, xylitol, or glycerol (propane-1,2,3-triol); an acetate ester of glycerol selected from the group consisting of monoacetate, diacetate, and triacetate of glycerol; triethyl citrate; dibutyl sebacate; and dibutyl phthalate; and mixtures thereof.

[0030] In some embodiments, the plasticizer is selected from the group consisting of glycerol, propylene glycol, ethylene glycol, sorbitol, triethyl citrate; and mixtures thereof.

[0031] In some embodiments, the compositions according to the present invention further comprise a cationic salt.

[0032] In some embodiments, the cationic salt is selected from the group consisting of: calcium salts, magnesium salts; and mixtures thereof.

[0033] In some embodiments, the composition according to the present invention further comprises one or more components selected from the group consisting of: one or more surfactants, such as simethicone, sodium lauryl sulfate; one or more colorants; one or more flavoring agents; and mixtures thereof.

[0034] In some embodiments, the concentration of alginate in the composition according to the present invention is from about 0.2 to about 10 weight percent based on the total weight of the aqueous composition.

[0035] In some embodiments, the total amount of HPMC and / or MC is at a concentration of about 8 to about 25 wt % based on the total weight of the aqueous composition.

[0036] In some embodiments, the alginate is present in an amount of at least about 0.2 wt%, preferably at least about 0.5 wt%, more preferably at least about 0.9 wt%, based on the total weight of the aqueous composition.

[0037] In some embodiments, the HPMC and / or MC is present in an amount of at least about 8 wt%, preferably at least about 10 wt%, more preferably at least about 14 wt%, based on the total weight of the aqueous composition.

[0038] In some embodiments, water in the compositions according to the present invention is present in an amount of no more than about 96 wt %, preferably no more than about 92 wt %, more preferably no more than about 87 wt % based on the total weight of the aqueous composition.

[0039] In some embodiments, the composition according to the present invention has a gelling temperature (Tg) of the aqueous composition in the range of 15°C to 45°C. 凝胶 ).

[0040] In some embodiments, the composition according to the present invention has a viscosity in the range of about 500 to about 6000 mPa.s measured by a Brookfield RV viscometer using a Brookfield No. 2 spindle, at a temperature in the range of 9°C to 1°C below the gel temperature of the aqueous composition.

[0041] In some embodiments, the compositions according to the present invention are for use in providing sustained or targeted release of a pharmaceutically or nutritionally active ingredient.

[0042] In some embodiments, compositions according to the present invention are for use in providing delayed or enteric release of a pharmaceutically or nutraceutically active ingredient.

[0043] The present invention relates to aqueous compositions comprising an alginate with low viscosity (such as low MW alginate) and a low viscosity film-forming polymer (such as low MW hydroxypropyl methylcellulose or hydroxypropyl methylcellulose (HPMC)), methods for producing these compositions, and coated dosage forms and capsule shells made from these aqueous compositions for delayed release and / or enteric release applications.

[0044] Many actives and / or APIs cannot be released immediately under gastric conditions because they may cause irritation to the gastric mucosa, degrade in gastric acid, or react with gastric acid. Various known esterified cellulose ethers and polymethacrylates have been used as enteric polymers for pharmaceutical dosage forms, such as methylcellulose phthalate (MCP), hydroxypropylmethylcellulose phthalate (HPMCP), methylcellulose succinate (MCS) or hydroxypropylmethylcellulose acetate succinate (HPMCAS). These polymers are used for coating dosage forms, such as tablets, microgranules or capsules.

[0045] The inventors of the present invention have discovered a thermogelling polymer capsule shell that can be prepared from an aqueous composition comprising low MW sodium alginate and low MW HPMC. These materials provide delayed / enteric release without the need for additional gelling agents, and effectively avoid additional coating steps on the capsule. In addition, the blend of HPMC / sodium alginate of the present invention provides a similar gelling temperature but a lower viscosity, which will be beneficial to the capsule manufacturing process. The formed capsule shell can also undergo a second immersion in a hot CaCl2 solution to enhance film strength and enteric properties. When the molecular weight of sodium alginate is increased to a molecular weight higher than that of Manucol LD / LB, the film strength and enteric properties of the blend prepared will be further improved.

[0046] Gelation temperature (T 凝胶 ) is used herein in its standard meaning to refer to the temperature at which a blend according to the present invention undergoes reversible thermal gelation. 凝胶 It can be measured by methods known to those skilled in the art. In a preferred embodiment, T 凝胶 is the temperature measured at the minimum complex viscosity (|η*|) during heating.

[0047] These blends can also be used in coatings, microencapsulation and other film-forming applications.

[0048] An advantage of the present invention is that it provides aqueous delayed release / enteric release formulations and corresponding capsules / films that avoid multiple formulation steps and multiple coating steps.

[0049] Alginate

[0050] The term "alginate" means a linear unbranched polymer containing (1-4)-linked β-D-mannuronic acid (M) and α-L-guluronic acid (G) residues. Alginate is found in brown seaweed (class, Phaeophyceae) and other sources. Alginate is not a random copolymer, but consists of blocks of similar and alternating residues (e.g., MMMM, GGGG, and GMGM), and is generally available in the form of alginic acid or its salts. The M ratio of alginates from Phaeophyceae seaweeds varies, and includes Lessonia nigrescens (53%-60% M), Laminaria digitata (about 59% M), Macrocystis pyrifera (about 60% M), Ecklonia maxima, and Laminaria saccharina.

[0051] The term alginate also refers to alginic acid, its salts and esters, such as sodium alginate, potassium alginate, and other monovalent alginates.

[0052] The alginate that can be suitably used according to the present invention is capable of forming a low viscosity aqueous solution at a concentration of 1% (w / v) at room temperature. More specifically, the alginate used according to the present invention is such an alginate that, after being dissolved in water at a concentration of 1% (w / v) at a temperature of 20°C, forms an aqueous solution with a viscosity value of less than 200mPaS. According to one embodiment of the present invention, the viscosity measured for a 1% (w / v) aqueous solution of alginate is in the range between 2 and 200mPaS. According to an alternative embodiment, alginate is selected for preparing a film so that the viscosity of its 1% (w / v) aqueous solution is less than 100mPaS at a temperature of 20°C, and preferably in the range between 10 and 70mPaS. Viscosity measurements can be performed on a Brookfield viscometer (spindle No. 2) at 20rpm to 60rpm.

[0053] In some embodiments, the aqueous film-forming composition of the present invention contains an alginate having an average M content of 25%-62% by weight of the M and G content. In some embodiments, the average M content of the alginate (by weight of the M and G content) may be at least about 25%, 30%, 40%, 50%, 55%, 56% and no more than about 50%, 55%, 56%, 57%, 58%, 59%, 60%, 61% or 62%. The M content may also be in the range of 53% to 59% by weight of the M and G content.

[0054] The alginates used according to the present invention are typically obtained from a variety of alginate-producing seaweeds. The M content in the seaweeds can vary depending on their life cycle at the time of harvest, plant specificity, etc. Seaweeds generally considered to produce alginates with M contents suitable for the present invention include Giant kelp, Laminaria palmata, Giant kelp, Giant kelp, and Sugar kelp. It is also within the scope of the present invention to use a blend of alginates with various M contents, provided that the M content of all alginates in the blend has an average M content of 25%-62% M. The average M content in the alginates is typically determined by 1 H-NMR determination. Alginate can typically be extracted from seaweed using, for example, standard commercial extraction methods (such as aqueous methods, including acidic pretreatment followed by alkaline extraction). Such conventional techniques are incorporated herein by reference.

[0055] The extracted alginates of the present invention having an M content of 25%-62% M can have a high molecular weight and therefore a high viscosity, such as 200-1,000 cps in a 1% solution. Therefore, it may be necessary to degrade the alginate to obtain a suitable average viscosity. Degradation is typically accomplished by subjecting alginic acid to conventional heat treatment methods. These conventional methods are incorporated herein by reference.

[0056] Additional viscosity tests that may be used to identify preferred alginates to be practiced according to the present invention may be conducted at different alginate concentrations and / or at different temperatures.

[0057] Examples of suitable commercial grades of alginic acid include (viscosity of 1% solution):

[0058] Alginic acid HFD2 (Alginate Industries, UK), which typically has a viscosity of 15-25 centipoise (cps),

[0059] Protacid F 120 (Protan & Fagertun, Norway), which typically has a viscosity of 15-25 cps,

[0060] Kelacid (Kelco, USA), which typically has a viscosity of 10-20 cps, and

[0061] Algocean (Sobalg, France), which typically has a viscosity of 15-25 cps.

[0062] Examples of suitable commercial grades of sodium alginate include:

[0063] Manucol LD (IFF Corporation (formerly FMC BIOPOLYMER)), which typically has a viscosity of 10 cps,

[0064] Manucol LB (IFF Corporation (formerly FMC Biopolymers)), which typically has a viscosity of 20-100 cps (3% solution),

[0065] Manucol LF (IFF Corporation (formerly FMC BIOPOLYMER)), which typically has a viscosity of 20 cps,

[0066] Protanal LF 5 / 60 or LF 5 / 40 (Protan & Fagertun), both typically having a viscosity of 10 cps, and Protanal LF 5 / 120M, which typically has a viscosity of 20 cps,

[0067] Manucol LHF and Protanal LF 10 / 120, which typically have a viscosity of 40 cps.

[0068] An example of a partially neutralized alginic acid is the one designated PE III (Protan & Fagertun), which is approximately 50% neutralized and typically has a viscosity of 15 cps.

[0069] Various blends may also be used, such as blends of alginic acid or other grades of sodium alginate, such as, for example, a 40 / 60 blend of Manucol LF and Manucol LHF, which has a viscosity of 24 cps.

[0070] Film-forming polymers

[0071] Any suitable film-forming polymer may be used in accordance with the present invention as long as the viscosity is in the range of about 2 to about 20 mPaS measured as a 2 wt % solution in water at 20° C. Those skilled in the art will be aware of such suitable polymers.

[0072] Suitable film-forming polymers for use according to the present invention include low viscosity hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC), hypromellose 2910 (7%-12% HP, 28%-30% methoxyl groups), hypromellose 2906 (4%-7.5% HP, 27%-30% methoxyl groups), hypromellose 2208 (4%-12% HP, 19%-24% methoxyl groups), and hypromellose 1828 (23%-32% HP, 16.5%-20% methoxyl groups). Commercially available methylcellulose and hydroxypropyl methylcellulose include the METHOCEL (trademark) series from IFF, the Japanese Pharmacopoeia METOLOSE (trademark) series and the METOLOSE series for food additives from Shin-Etsu Chemical Co., Ltd., the AnyCoat-C or AnyAddy (trademark) series from Lotte (formerly Samsung) Fine Chemicals, and the Benecel (trademark) series from Ashland.

[0073] In the present disclosure, it is preferred to use a film-forming polymer having a "viscosity" of 2 mPa·s or more in the form of a 2 mass % aqueous solution at 20°C. "Viscosity" can be measured based on the portion of methylcellulose and hypromellose formulated based on the International Harmonization Plan in the 15th edition of the Pharmacopoeia and later. In other words, "viscosity" refers to the viscosity value (mPa·s) of a 2 mass % aqueous solution of water-soluble cellulose at 20°C±0.1°C.

[0074] Moreover, the viscosity (sometimes referred to as "viscosity grade value") marked by the manufacturer of the compound may be used as "viscosity". Regarding the marked viscosity and the range of the marked viscosity, for example, the METHOCEL (trademark) series from IFF Corporation or the METOLOSE (trade name) series from Shin-Etsu Chemical Co., Ltd. are described as having a viscosity value of 80% to 120% of the marked viscosity when the marked viscosity is less than 600 mPa·s, and having a viscosity value of 75% to 140% of the marked viscosity when the marked viscosity is 600 mPa·s or higher. Regarding the lower limit value of 2 mPa·s in the present invention, the marked viscosity may be directly used as "viscosity" as long as the purpose of the present invention is not impaired.

[0075] In the present disclosure, the preferred lower limit of the viscosity is 2 mPa·s, such as 4, 6, 8 or 10 mPa·s. The preferred upper limit of the viscosity is 20 mPa·s, such as 18, 16, 14, 12 or 10 mPa·s.

[0076] Plasticizers

[0077] Examples of plasticizers include surfactants such as sucrose fatty acid esters, glycerol fatty acid esters, monoglycerol fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc.; esters of citric acid such as triethyl citrate (TEC); polyols such as glycerol, propylene glycol, polyethylene glycol, etc.; glucose, sugars such as fructose and glucose liquid sugars, sugars such as sucrose; sugar alcohols such as sorbitol, maltitol, mannitol, erythritol, xylitol; dodecanol, tridecanol, tetradecanol, pentadecyl alcohol, hexadecanol, heptadecanol, octadecyl alcohol; higher alcohols such as hexadecanol, isostearyl alcohol, 2-octyldodecanol, etc. (preferably having 6 to 22 carbon atoms); and oils and fats such as medium-chain fatty acid esters (preferably having 6 to 12 carbon atoms). It is described below. These plasticizers can be used alone or in combination of two or more.

[0078] The term "capsule" means a closed structure having contents (fill material) and a surface (membrane). When substantially dry, the membrane constrains the fill material. Preferably, the membrane disintegrates under conditions found in the small intestine of a mammal. The finished capsule is substantially dry after being exposed to excess gas at 30% or less relative humidity at room temperature for one day (or equivalent conditions). Dry means substantially dry. A capsule is "wet" when it is not substantially dry or when it is substantially in contact with an aqueous solution.

[0079] Experimental Section

[0080] Example 1

[0081] Examples of formulations with alginate are shown in Table 1, Table 2 and Table 3. The rheology of the formulations of the invention listed in Table 1 and Table 2 is shown in Figure 1 The viscosity of the preparation of the present invention showed a lower viscosity than that of the commercial HPMC capsule material. In addition, the preparation of the present invention showed a gelation temperature and gel strength similar to those of the commercial HPMC capsule material. All film samples Ex0217-1LD, Ex0217-2LD, Ex0217-1, and Ex0701LD-1 showed good film strength. Figure 2 as shown in .

[0082] The delayed and enteric performance of the films were performed using a USP dissolution apparatus 2 with a 100 mL vessel and mini-paddles.

[0083] Device Configuration: Modified USPII-with 1000mL container and paddle

[0084] Dissolution medium: 100 mL degassed pH 1.2 HCl buffer

[0085] Temperature: 37℃±0.5℃

[0086] Stirring speed: 50RPM

[0087] All membrane samples Ex0217-1LD, Ex0217-2LD, Ex0217-1, and Ex0701LD-1 showed integrity after 2 hours in pH 1.2 dissolution medium. Figure 3 as shown in .

[0088] Table 1. Delayed release formulations of HPMC and Na alginate blends.

[0089]

[0090] Table 2. Delayed release formulations of HPMC and Na alginate blends.

[0091] sample Ex0217-1, score <![CDATA[METHOCEL TM F4 Pr]]> 0.15 Manucol LB 0.01 TEC 0.004 Deionized water 0.836 total 1.0000

[0092] Table 3. Delayed release formulations of HPMC and Na alginate blends.

[0093] sample Ex0701LD-1, score <![CDATA[METHOCEL TM F4 Pr]]> 0.16 Manucol LD 0.012 CaCl2 0.0005 TEC 0.0048 Deionized water 0.818 total 1.0000

Claims

1. An aqueous film-forming composition comprising: a) an alginate having a viscosity in the range of about 2 to about 200 mPaS measured as a 1 wt% solution in water at 20°C; and b) a film-forming polymer having a viscosity in the range of about 2 to about 20 mPaS measured as a 2 wt% solution in water at 20°C.

2. The composition according to claim 1, wherein The alginate is selected from the group consisting of sodium alginate, potassium alginate, and other monovalent alginates; and mixtures thereof.

3. The composition according to any one of claims 1 to 2, wherein The alginate is sodium alginate.

4. The composition according to any one of claims 1 to 3, wherein The alginate has a viscosity in the range of about 2 to about 100 mPaS, more preferably in the range of about 2 to about 30 mPaS, measured as a 1 wt% solution in water at 20°C.

5. The composition according to any one of claims 1 to 4, wherein The film-forming polymer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC) and methyl cellulose (MC), hydroxypropyl cellulose (HPC); and mixtures thereof.

6. The composition according to any one of claims 1 to 5, wherein The film-forming polymer has a viscosity in the range of about 3 to about 15 mPaS, more preferably in the range of about 3 to about 7 mPaS, measured as a 2 wt% solution in water at 20°C.

7. The composition according to any one of claims 1 to 6, wherein The viscosity is measured using a Brookfield RV viscometer using a Brookfield No. 2 spindle.

8. The composition according to any one of claims 1 to 7, wherein The film-forming polymer is selected from the following group: Hydroxypropyl methylcellulose 2910 (7%-12% HP, 28%-30% methoxy), Hydroxypropyl methylcellulose 2906 (4%-7.5% HP, 27%-30% methoxy), Hydroxypropyl methylcellulose 2208 (4%-12% HP, 19%-24% methoxy), Hydroxypropyl methylcellulose 1828 (23%-32% HP, 16.5%-20% methoxy), methylcellulose; and mixtures thereof.

9. The composition according to any one of claims 1 to 8, further comprising a plasticizer.

10. The composition according to claim 9, wherein The plasticizer is selected from the group consisting of: a polyol, such as a sugar alcohol, such as propylene glycol, ethylene glycol, sorbitol, mannitol, erythritol, xylitol, or glycerol (propane-1,2,3-triol); an acetate ester of glycerol selected from the group consisting of monoacetate, diacetate and triacetate of glycerol; triethyl citrate; dibutyl sebacate; and dibutyl phthalate; and mixtures thereof.

11. The composition according to any one of claims 9 to 10, wherein The plasticizer is selected from the group consisting of glycerol, propylene glycol, ethylene glycol, sorbitol, triethyl citrate; and mixtures thereof.

12. The composition according to any one of claims 1 to 11, further comprising a cationic salt.

13. The composition according to claim 12, wherein The cationic salt is selected from the group consisting of: calcium salts, magnesium salts; and mixtures thereof.

14. The composition according to any one of claims 1 to 11, further comprising one or more components selected from the group consisting of: one or more surfactants, such as dimethicone, sodium lauryl sulfate; one or more colorants; one or more flavoring agents; and mixtures thereof.

15. The composition according to any one of claims 1 to 14, wherein The concentration of alginate is from about 0.2 to about 10 weight % based on the total weight of the aqueous composition.

16. The composition according to any one of claims 1 to 15, wherein The total amount of HPMC and / or MC may be present in a concentration of about 8 to about 25 wt % based on the total weight of the aqueous composition.

17. The composition according to any one of claims 1 to 16, wherein The alginate is present in an amount of at least about 0.2 wt %, preferably at least about 0.5 wt %, more preferably at least about 0.9 wt %, based on the total weight of the aqueous composition.

18. The composition according to any one of claims 1 to 17, wherein The HPMC and / or MC is present in an amount of at least about 8 wt%, preferably at least about 10 wt%, more preferably at least about 14 wt%, based on the total weight of the aqueous composition.

19. The composition according to any one of claims 1 to 18, wherein Water is present in an amount of no more than about 96 wt %, preferably no more than about 92 wt %, more preferably no more than about 87 wt %, based on the total weight of the aqueous composition.

20. The composition according to any one of claims 1 to 13, having a gelling temperature (Tg) of the aqueous composition in the range of 15°C to 45°C. 凝胶 ).

21. The composition of any one of claims 1 to 20, having a viscosity in the range of about 500 to about 6000 mPa.s measured by a Brookfield RV viscometer using a Brookfield No. 2 spindle at a temperature in the range of 9°C to 1°C below the gel temperature of the aqueous composition.

22. A composition according to any one of claims 1 to 21 for use in providing sustained or targeted release of a pharmaceutically or nutritionally active ingredient.

23. A composition according to any one of claims 1 to 21 for use in providing delayed or enteric release of a pharmaceutically or nutraceutically active ingredient.

24. Use of the composition according to any one of claims 1 to 21 for encapsulating drugs, probiotics, nutritional supplements or food supplements or a combination thereof.

25. A capsule film made from the composition according to any one of claims 1 to 21.

26. A capsule shell comprising: a) an alginate having a viscosity in the range of about 2 to about 200 mPaS measured as a 1 wt% solution in water at 20°C; and b) a film-forming polymer having a viscosity in the range of about 2 to about 20 mPaS measured as a 2 wt% solution in water at 20°C.

27. The capsule shell according to claim 26, which is a hard capsule shell.

28. A capsule shell according to any one of claims 26 to 27, prepared from a composition according to any one of claims 1 to 21.

29. A capsule comprising a capsule shell prepared from the composition according to any one of claims 1 to 21.

30. The capsule of claim 29, further comprising a filling material comprising a pharmaceutically active ingredient, a dietary supplement, a flavoring agent, a foodstuff, an agricultural chemical, or a fragrance.

31. Capsules according to any one of claims 29 to 30, which, after having been formed, may optionally be immersed in one or more hot aqueous CaCl2 or ethanol / water solutions.

32. A method for producing a capsule membrane, a capsule shell, or a capsule, the method comprising the steps of: An aqueous composition according to any one of claims 1 to 21 is provided, preheating a mold pin to a temperature of ±5°C of the maximum viscosity point of the aqueous composition higher than the gelling temperature, dipping the preheated mold pin into the aqueous composition at a temperature lower than the gelling temperature, forming a film on the pin by removing the mold pin from the composition, and drying the film on the mold pin at a temperature higher than the gelling temperature.

33. The method of claim 32, wherein: The capsule membrane, capsule shell or capsule is as defined in any one of claims 25 to 31.

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