A film-forming composition and its use, soft capsules and methods of preparation

Abstract

The application discloses a film-forming composition and application thereof, a soft capsule and a preparation method, and belongs to the technical field of soft capsule preparation, and aims to provide a film-forming composition with high strength, high toughness, low oil permeation and enteric solubility; the film-forming composition comprises, in mass fraction, 0.1%-0.3% of gellan gum, 30%-38% of hydroxypropyl starch, 1.0%-1.8% of oat beta-glucan, 0.5%-1.2% of pullulan, 20%-28% of a plasticizer and the balance of water; and the plasticizer is at least one of glycerol, sorbitol, maltitol and enzymatic gluten.

Description

Technical Field

[0001] This invention belongs to the field of soft capsule preparation technology, and relates to a film-forming composition and its application, soft capsules and preparation methods. Background Technology

[0002] As a mainstream drug delivery form for pharmaceuticals and functional oils, soft capsules, while possessing excellent film-forming properties and toughness, have significant drawbacks: gelatin, derived from animal skin and bones, is unsuitable for vegetarians, halal individuals, and those practicing religious faiths; furthermore, gelatin readily undergoes cross-linking reactions with aldehyde drugs, leading to hardening and disintegration of the capsule shell; and oily contents are prone to oil leakage and oxidative deterioration during long-term storage, with animal disease risks present during the production process. With the continued growth in demand for plant-based pharmaceutical excipients, plant-based soft capsule shells have become a mainstream research and development direction in the industry.

[0003] Existing plant-based soft capsule film-forming systems mostly use a combination of single starch and single plant gum to prepare the film material, which generally has multiple defects: First, pure starch films have poor mechanical properties, low tensile strength, insufficient elongation at break, and are extremely prone to brittleness in low-temperature drying environments, resulting in a high breakage rate during transportation and storage; Second, single gel systems have sparse cross-linked networks and large membrane pores, resulting in poor barrier effects against oily contents, easy leakage during long-term storage, and easy penetration of oxygen and moisture into the capsule, accelerating the oxidation and yellowing of the contents, leading to a short product shelf life; Third, conventional plant films have insufficient acid resistance, and when used in enteric formulations, they easily soften, crack, and leak after immersion in artificial gastric juice for 2 hours, failing to meet the requirements of enteric coating that is insoluble in the stomach and targets drug release in the intestine; Fourth, the formulations rely heavily on small molecule polyols such as glycerol and sorbitol as plasticizers, and during long-term storage, these small molecule plasticizers continuously migrate and precipitate, causing the capsule shell to harden and become sticky, significantly reducing its appearance and stability in use.

[0004] Patent document CN121647378A (publication date March 13, 2026) discloses a chewable plant-based soft capsule shell, which, by weight, comprises 8-15 parts of compound starch, 0.3-0.8 parts of pullulan, 0.3-0.8 parts of carrageenan, 0.6-1 parts of gellan gum, 1-1.5 parts of konjac flour, 5-8 parts of mannitol, 5-10 parts of sorbitol, 10-20 parts of compound fiber, and 50-70 parts of water. This invention overcomes the defects of low tensile strength and high water sensitivity of the capsule shell, and is beneficial to improving the elasticity and stability of the capsule shell. However, this invention is not suitable for enteric-coated formulations.

[0005] Patent document CN122096407A (published on May 29, 2026) discloses a yeast polysaccharide soft capsule shell, comprising the following components by weight: 40 parts gelatin, 20 parts glycerin, 2 parts yeast insoluble β-glucan, and 3 parts yeast mannan oligosaccharide. This invention can effectively improve the stability problems of soft capsule products, such as adhesion, oil leakage, and hardening of the capsule shell, which are prone to occur during the shelf life. However, this invention contains gelatin and is not a plant-based soft capsule.

[0006] There is currently a huge market gap for plant-based soft capsule products, and there is an urgent need to provide a soft capsule that is made entirely of plants and has the advantages of high strength, high toughness, acid resistance, enteric coating, and low oil permeability. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides a film-forming composition and its application, soft capsules, and preparation method. The film-forming composition exhibits high strength, high toughness, resistance to oil leakage, and enteric stability, thus overcoming the deficiencies of existing technologies.

[0008] Terminology Explanation: Unless otherwise defined, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this subject matter pertains. Unless otherwise stated, all patents, patent inventions, and disclosures cited throughout this document are incorporated herein by reference in their entirety. Where multiple definitions exist for terms herein, the definitions provided in this chapter shall prevail.

[0009] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0010] The definitions of standard chemical terms can be found in the reference "Chinese Pharmacopoeia 2025 Edition".

[0011] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0012] The “range” disclosed in this document takes the form of a lower limit and an upper limit. It can be one or more lower limits and one or more upper limits, respectively. A given range is defined by selecting a lower limit and an upper limit. The selected lower and upper limits define the boundaries of the particular range. All ranges that can be defined in this way are inclusive and composable; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is also expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if the minimum range values ​​are listed as 1 and 2, and if the maximum ranges are listed as 3, 4, and 5, then the following ranges are all expected: 1-2, 1-4, 1-5, 2-3, 2-4, and 2-5.

[0013] In this invention, unless otherwise specified, the numerical range "ab" represents a shortened representation of any combination of real numbers from a to b, where a and b are both real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" have been listed in this document, and "0-5" is simply a shortened representation of these numerical combinations.

[0014] The terms “optional / arbitrary” or “optionally / arbitrarily” mean that the event or situation described below may or may not occur, including both the occurrence and non-occurrence of the event or situation.

[0015] As used herein, the term "room temperature" refers to ambient temperature, ranging from about 10°C to about 40°C. In some embodiments, "room temperature" refers to a temperature ranging from about 20°C to about 30°C; in other embodiments, "room temperature" refers to a temperature ranging from about 25°C to about 30°C; and in still other embodiments, "room temperature" refers to 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc.

[0016] As used in this article, "solid-liquid separation" refers to the process of separating a mixture containing solid particles and liquid components into independent solid and liquid phases using physical or mechanical methods. This process can remove solid impurities, cell debris, precipitates, microbial aggregates, and other solid substances from the mixture, obtaining a clear liquid phase or collecting the target solid product. It is a commonly used separation and purification method in cell culture, sample pretreatment, and reagent preparation. It includes, but is not limited to, centrifugation, filtration, sedimentation, and pressure filtration. The term "enzyme inactivation" as used in this article refers to the conventional operation of causing irreversible spatial conformational denaturation of the protease in the system after the enzymatic hydrolysis reaction has reached the preset hydrolysis time, thereby permanently losing its catalytic activity for peptide bond hydrolysis; including but not limited to high-temperature water bath inactivation, steam heating inactivation, etc.

[0017] The term "drying" as used in this article refers to the routine operation of removing free moisture or organic solvents from materials by controlling environmental conditions such as temperature, airflow, and pressure, thereby reducing the moisture content of the materials and maintaining the stability of the physicochemical properties of the formulation, including but not limited to hot air drying, vacuum drying, low-temperature air drying, fluidized bed drying, etc.

[0018] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a film-forming composition comprising, by mass fraction: 0.1%-0.3% gellan gum, 30%-38% hydroxypropyl starch, 1.0%-1.8% oat β-glucan, 0.5%-1.2% pullulan, 20%-28% plasticizer, and the balance being water.

[0019] In some embodiments, the plasticizer is at least one of glycerol, sorbitol, maltitol, and enzymatically hydrolyzed gluten.

[0020] In some embodiments, the enzymatically hydrolyzed gluten is prepared by enzymatic hydrolysis of gluten powder.

[0021] Preferably, the method for preparing the enzymatically hydrolyzed gluten protein is as follows: gluten powder and water are mixed, protease is added for enzymatic hydrolysis, the hydrolysate is separated into solid and liquid components, and the clear liquid is dried.

[0022] More preferably, the protease is at least one of fig protease, papain, pepsin, chymotrypsin, trypsin, bromelain, Trichoderma listeri protease, Bacillus subtilis protease, Aspergillus honey protease, Aspergillus oryzae protease, and Aspergillus niger protease.

[0023] More preferably, the amount of protease used is 0.5%-2% of the mass of gluten powder; for example, the amount of protease used can be selected as 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, or a range derived therefrom.

[0024] More preferably, the enzymatic hydrolysis time is 4-8 hours; for example, the enzymatic hydrolysis time can be selected as 4.0 hours, 4.5 hours, 5.0 hours, 5.5 hours, 6.0 hours, 6.5 hours, 7.0 hours, 7.5 hours, 8.0 hours, or a range derived therefrom.

[0025] More preferably, the amount of water used is 8-12 times the mass of the gluten powder; for example, the amount of water can be selected as 8 times, 9 times, 10 times, 11 times, 12 times, or a range derived therefrom.

[0026] In some embodiments, the plasticizer is sorbitol and enzymatically hydrolyzed gluten; preferably, the mass ratio of sorbitol to enzymatically hydrolyzed gluten is 3-8:1; for example, the mass ratio of sorbitol to enzymatically hydrolyzed gluten can be selected as 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, or a range derived therefrom.

[0027] In some embodiments, the amount of gellan gum in the film-forming composition, by mass fraction, may be selected as 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.30%, or a range derived thereof.

[0028] In some embodiments, the amount of hydroxypropyl starch in the film-forming composition, by mass fraction, may be 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, or a range derived thereof.

[0029] In some embodiments, the amount of oat β-glucan in the film-forming composition may be selected as 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or a range derived thereof, by mass fraction.

[0030] In some embodiments, the amount of pullulan in the film-forming composition, by mass fraction, may be 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, or a range derived thereof.

[0031] In some embodiments, the amount of plasticizer in the film-forming composition, by mass fraction, may be selected as 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, or a range derived thereof.

[0032] In some embodiments, the film-forming composition comprises, by mass fraction: 0.25% gellan gum, 34% hydroxypropyl starch, 1.5% oat beta-glucan, 1% pullulan, 24% plasticizer, and the balance being water.

[0033] Secondly, the present invention provides a method for preparing the above-mentioned film-forming composition, comprising the following steps: (1) Add gellan gum, oat β-glucan and pullulan to the plasticizer and stir evenly to obtain a premix; (2) Add water to the premix and heat to dissolve it to obtain a sol solution; (3) Adjust the pH of the sol solution to 5.5-6.5, then add hydroxypropyl starch and homogenize.

[0034] In some implementations, the heating in step (2) is to heat to 60-90°C.

[0035] In some implementations, the pH adjuster used to adjust the pH in step (3) is citric acid.

[0036] Thirdly, the present invention provides the application of the above-described film-forming composition or the film-forming composition prepared by the above-described preparation method in the preparation of soft capsules.

[0037] Fourthly, the present invention provides: a soft capsule comprising a soft capsule shell and contents, wherein the soft capsule shell is prepared from the above-described film-forming composition or a film-forming composition prepared by the above-described preparation method.

[0038] Fifthly, the present invention provides a method for preparing a soft capsule, comprising the following steps: S1. Degas the film-forming composition to obtain a gel. S2. Press the gel and its contents into shape to obtain the final product.

[0039] The present invention has at least the following beneficial effects: 1. This invention employs a quaternary natural polysaccharide compound consisting of gellan gum, hydroxypropyl starch, oat β-glucan, and pullulan. Gellan gum forms the main gel framework, providing basic membrane strength; hydroxypropyl starch fills the gel network and regulates the pore structure; oat β-glucan self-assembles through molecular hydrogen bonds to form a three-dimensional network structure, serving as a flexible phase interwoven within the main network; pullulan reinforces the overall structure by winding, enhancing oil-blocking, oxygen-blocking, and anti-aging capabilities. The synergistic effect of each component results in a film-forming composition with high strength, high toughness, good molding effect, and minimal oil leakage. Simultaneously, the system exhibits excellent acid resistance, enabling stable enteric-coated drug release.

[0040] 2. The present invention introduces enzymatically hydrolyzed gluten protein, which can form a protein-polysaccharide interpenetrating double network with the tetravalent polysaccharide in the system, thereby improving the tensile toughness of the capsule shell and reducing oil leakage.

[0041] 3. Experiments have shown that the soft capsules prepared by the film-forming composition of the present invention have good comprehensive properties such as high strength, high toughness, acid resistance to enteric coating, and low oil permeability.

[0042] 4. The raw materials of the film-forming composition of the present invention are all natural plant excipients, which are safe and compliant, and the production cost is controllable. They are very suitable for the preparation of plant-based enteric soft capsules and have broad application prospects. Attached Figure Description

[0043] Figure 1The image shows the appearance of the krill oil soft capsules prepared according to an embodiment of the present invention. Detailed Implementation

[0044] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0045] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0046] All numerical values ​​or expressions relating to component amounts, process conditions, etc., used in this invention shall be understood to be modified by the word "about" in all cases. When referring to a quantity or range of values, the quantity or range is an approximation within experimental variability (or within statistical experimental error). In this invention, the term "about" shall have the meaning of being within 10%, preferably within 5%, of the specified value or range.

[0047] Unless otherwise specified, percentages in this invention refer to mass percentages, temperatures refer to room temperature, and solvents refer to water.

[0048] For example, the gellan gum is a low-acyl gellan gum, TW-JY800, purchased from Zhejiang Tianwei Biotechnology Co., Ltd.; hydroxypropyl starch, purchased from Hubei Huada Fine Chemical Co., Ltd.; oat β-glucan, purchased from Pinhong Biotechnology, water soluble 80%; pullulan, qy4000420, purchased from Qiyuan (Guangdong) Pharmaceutical Chemical Co., Ltd.; gluten powder, purchased from Hubei Rishengchang New Material Technology Co., Ltd.; bromelain 300U / mg; krill oil, P50, purchased from Qingdao Antarctic Weikang Biotechnology Co., Ltd.

[0049] Example 1 A film-forming composition comprising, by mass fraction: 0.3% gellan gum, 30% hydroxypropyl starch, 1.0% oat β-glucan, 1.2% pullulan, 28% plasticizer, and the balance being water; The plasticizer is sorbitol and enzymatically hydrolyzed gluten in a mass ratio of 8:1; The preparation method of the enzymatically hydrolyzed gluten protein is as follows: add 12 times the weight of water to gluten powder and stir at 3000 rpm for 40 min. Add 2% of bromelain by weight of gluten powder. Enzymatically hydrolyze at pH 6.5-7 and 55℃ for 4 h. Inactivate the enzyme at 85℃ for 20 min. Centrifuge the enzymatic hydrolysate at 3000 rpm for 10 min. Dry the supernatant under reduced pressure and vacuum (50℃, -0.09MPa) for 14 h.

[0050] The preparation method of the film-forming composition is as follows: (1) Add gellan gum, oat β-glucan and pullulan to the plasticizer and stir evenly to obtain a premix; (2) Add water to the premix, heat to 60°C, and stir at 500 rpm to dissolve, thus obtaining a sol solution; (3) Adjust the pH of the sol solution to 5.5-6.5 with 0.3% citric acid by mass, then add hydroxypropyl starch and stir to homogenize.

[0051] The preparation method of krill oil soft capsules is as follows: The above film-forming composition is degassed to obtain a gel. The gel liquid is then fed into a soft capsule machine and pressed with krill oil to form a soft capsule with a specification of 1g / capsule.

[0052] Example 2 A film-forming composition comprising, by mass fraction: 0.1% gellan gum, 38% hydroxypropyl starch, 1.8% oat β-glucan, 0.5% pullulan, 20% plasticizer, and the balance being water; The plasticizer is sorbitol and enzymatically hydrolyzed gluten in a mass ratio of 3:1; The preparation method of the enzymatically hydrolyzed gluten protein is as follows: add 8 times the weight of water to gluten powder and stir at 3000 rpm for 40 min. Add 0.5% of bromelain by weight of gluten powder. Enzymatically hydrolyze at pH 6.5-7 and 55℃ for 8 h. Inactivate the enzyme at 85℃ for 20 min. Centrifuge the hydrolysate at 3000 rpm for 10 min. Dry the supernatant under reduced pressure and vacuum (50℃, -0.09MPa) for 14 h.

[0053] The preparation method of the film-forming composition is as follows: (1) Add gellan gum, oat β-glucan and pullulan to the plasticizer and stir evenly to obtain a premix; (2) Add water to the premix, heat to 90°C, and stir at 500 rpm to dissolve, thus obtaining a sol solution; (3) Adjust the pH of the sol solution to 5.5-6.5 with 0.3% citric acid by mass, then add hydroxypropyl starch and stir to homogenize.

[0054] The preparation method of krill oil soft capsules is as follows: The above film-forming composition is degassed to obtain a gel. The gel liquid is then fed into a soft capsule machine and pressed with krill oil to form a soft capsule with a specification of 1g / capsule.

[0055] Example 3 A film-forming composition comprising, by mass fraction: 0.25% gellan gum, 34% hydroxypropyl starch, 1.5% oat β-glucan, 1% pullulan, 24% plasticizer, and the balance being water; The plasticizer is sorbitol and enzymatically hydrolyzed gluten in a mass ratio of 5:1; The preparation method of the enzymatically hydrolyzed gluten protein is as follows: add 10 times the weight of water to gluten powder and stir at 3000 rpm for 40 min. Add 1% of bromelain by weight of gluten powder. Enzymatically hydrolyze at pH 6.5-7 and 55℃ for 6 h. Inactivate the enzyme at 85℃ for 20 min. Centrifuge the enzymatic hydrolysate at 3000 rpm for 10 min. Dry the supernatant under reduced pressure and vacuum (50℃, -0.09 MPa) for 14 h.

[0056] The preparation method of the film-forming composition is as follows: (1) Add gellan gum, oat β-glucan and pullulan to the plasticizer and stir evenly to obtain a premix; (2) Add water to the premix, heat to 80°C, and stir at 500 rpm to dissolve, thus obtaining a sol solution; (3) Adjust the pH of the sol solution to 5.5-6.5 with 0.3% citric acid by mass, then add hydroxypropyl starch and stir to homogenize.

[0057] The preparation method of krill oil soft capsules is as follows: The above film-forming composition is degassed to obtain a gel. The gel liquid is then fed into a soft capsule machine and pressed with krill oil to form a soft capsule with a specification of 1g / capsule.

[0058] Comparative Example 1 The difference between this comparative example and Example 3 is that it does not contain oat β-glucan.

[0059] Specifically, a film-forming composition comprises, by mass fraction: 0.25% gellan gum, 35.5% hydroxypropyl starch, 1% pullulan, 24% plasticizer, and the balance being water; Everything else is the same as in Example 3.

[0060] Comparative Example 2 The difference between this comparative example and Example 3 is that the plasticizer does not contain enzymatically hydrolyzed gluten.

[0061] Specifically, a film-forming composition comprises, by mass fraction: 0.25% gellan gum, 34% hydroxypropyl starch, 1.5% oat β-glucan, 1% pullulan, 24% plasticizer, and the balance being water; The plasticizer is sorbitol and maltitol in a mass ratio of 5:1.

[0062] Everything else is the same as in Example 3.

[0063] Comparative Example 3 The difference between this comparative example and Example 3 is that the plasticizer is different.

[0064] Specifically, a film-forming composition comprises, by mass fraction: 0.25% gellan gum, 34% hydroxypropyl starch, 1.5% oat β-glucan, 1% pullulan, 24% plasticizer, and the balance being water; The plasticizer is sorbitol and enzymatically hydrolyzed gluten in a mass ratio of 1:1.

[0065] Everything else is the same as in Example 3.

[0066] Detection Example 1 Compression fracture test Five krill oil soft capsules were randomly selected, all of which were intact and undamaged. Their appearance was as follows: Figure 1 As shown. The capsules were left at room temperature for 24 hours to equilibrate moisture. The compressive strength of the soft capsules was then tested using a texture analyzer.

[0067] Preloading speed: 1.0 mm / s; Test compression speed: 0.5 mm / s (Pharmacopoeia standard); Trigger force: 5g; Termination method: Press until the capsule is completely ruptured, record the peak rupture force; complete 5 parallel tests, remove abnormal data, and calculate the average value.

[0068] The results are shown in Table 1.

[0069] Table 1. Average bursting force (N) of krill oil soft capsules

[0070] The results showed that the average breaking force of the krill oil soft capsules prepared in Examples 1-3 of this invention was 30.2-36.9 N, which was higher than that of commercially available krill oil soft capsule products. This indicates that compared with the prior art, the film-forming composition of this invention can significantly improve the mechanical strength of the capsule shell, has stronger resistance to compression and breakage, and lower risk of breakage during storage and transportation.

[0071] Comparing Example 3 with Comparative Examples 2 and 3, it can be seen that the lack of enzymatically hydrolyzed gluten in the film-forming composition or the excessively high proportion of enzymatically hydrolyzed gluten will lead to a deterioration in the overall mechanical strength of the capsule.

[0072] Comparing Example 3 and Comparative Example 1, it can be seen that oat β-glucan in the film-forming composition can synergistically improve the toughness and pressure resistance of the capsule shell.

[0073] Detection Example 2 Method for determining the disintegration time of enteric-coated soft capsules (based on General Chapter 0921 of the Chinese Pharmacopoeia 2025) I. Detection Principle The test is conducted in two steps: an acid-resistant phase and an enteric-disintegration phase. First, the drug does not rupture or leak in the acidic environment of the stomach for 2 hours. Then, it completely disintegrates and dissolves in the weakly alkaline environment of the intestine within 1 hour, ensuring that the drug is released into the intestine instead of the stomach.

[0074] II. Instruments and Reagents 1. Instruments The device includes a lift-type disintegration time limit meter, a matching 6-hole basket, a standard baffle, a constant temperature water bath, a pH meter, and a timer.

[0075] 2. Preparation of standard media 1) Hydrochloric acid solution (9→1000, artificial gastric juice, pH≈1.2): Take 9 mL of hydrochloric acid, dilute with water to 1000 mL, mix well, and calibrate the pH.

[0076] 2) Artificial intestinal fluid (pH 6.8 phosphate buffer): Dissolve 6.8g of potassium dihydrogen phosphate in 500mL of water, and adjust the pH to 6.8 with 0.4% NaOH; separately dissolve 10g of trypsin in water, combine the two solutions and make up to 1000mL. Prepare fresh or store at low temperature, and warm to 37℃ before testing.

[0077] 3. Sample Requirements Six finished krill oil soft capsules were randomly selected. They were found to be intact, without any visible cracks, leakage, or adhesion.

[0078] III. Operating Procedures Phase 1: Acid resistance test (hydrochloric acid solution, without baffle, 2 hours) 1. Add 1000mL of hydrochloric acid solution to the disintegration apparatus beaker, turn on the apparatus and heat it to a constant temperature of 37℃±0.5℃; 2. Place one krill oil soft capsule in each of the six glass tubes in the hanging basket, without adding any baffles throughout the process; 3. When the basket is lowered to its lowest point, the screen is 25mm from the bottom of the beaker; when it is raised to its highest point, the screen is 15mm below the liquid surface. 4. Start the lifting and lowering process and run continuously for 2 hours, visually observing the status of each particle throughout the entire process.

[0079] Phase 1 qualification criteria: All 6 capsules must meet the following criteria: no cracks, no shell ruptures, no leakage of contents, and no obvious softening or collapse. If any one capsule shows cracking, leakage, or shell breakage, it will be deemed unqualified for acid resistance.

[0080] Phase 2: Intestinal fluid disintegration test (pH 6.8 artificial intestinal fluid, with baffle, 1 h) After 1.2 hours of acid resistance, remove the entire basket and quickly rinse the tube wall and capsule surface with a small amount of purified water to remove residual hydrochloric acid. 2. Replace the medium in the beaker with artificial intestinal fluid preheated to 37℃±0.5℃; 3. Place one standard baffle inside each glass tube (to hold down the soft capsule and prevent it from floating). 4. Reset the basket, start the instrument's lifting and lowering mechanism, and begin timing. The maximum observation time is 60 minutes.

[0081] Disintegration endpoint determination: The capsule shell completely dissolves and shatters, and the contents are completely released; except for trace amounts of insoluble enteric coating fragments, everything passes through the bottom sieve; a small amount of light, soft residue without a hard core is considered to be completely disintegrated.

[0082] IV. Result Determination Rules 1. Initial test of 6 tablets: The acid phase remained intact for 2 hours, and the intestinal fluid completely disintegrated within 60 minutes, indicating that the test was satisfactory; 2. In the initial test, only one capsule failed to disintegrate on time: six more capsules were taken for retesting. All six capsules passed the retest, and the entire batch was deemed qualified. 3. If ≥2 capsules fail to disintegrate within the intestinal fluid time limit or if any one capsule cracks and leaks during the acid phase, the test is deemed unqualified and no retest is required.

[0083] The results are shown in Table 2.

[0084] Table 2. Acid resistance and disintegration results of krill oil soft capsules

[0085] Note: " / " in the table indicates that it was not detected.

[0086] The results showed that all the krill oil soft capsules prepared in Examples 1-3 of this invention passed the 2-hour artificial gastric juice acid resistance test without softening, leakage, or cracking, and the average intestinal fluid disintegration time was only 33.5-39.7 min, which meets the pharmacopoeia standard for enteric-coated preparations and can achieve gastric insolubility and targeted intestinal drug release.

[0087] Comparing Example 3 with Comparative Examples 1 and 2, it is evident that the lack of oat β-glucan or enzymatically hydrolyzed gluten in the film-forming composition significantly degrades the acid resistance of the krill oil soft capsules, preventing them from meeting the requirements for enteric coating. This demonstrates that oat β-glucan and enzymatically hydrolyzed gluten synergistically improve membrane density and enhance acid resistance; both are indispensable.

[0088] Comparing Example 3 and Comparative Example 3, it can be seen that the increased content of enzymatically hydrolyzed gluten in the film-forming composition prolongs the average disintegration time of intestinal fluid to 51.2 min, indicating that excessive addition of enzymatically hydrolyzed gluten will slow down the dissolution rate of the capsule shell in the intestine, which is not conducive to rapid drug release.

[0089] Detection Example 3 Long-term storage oil leakage rate test Take 50 krill oil soft capsules, seal them in an aluminum-plastic bag, and store them in a constant temperature and humidity chamber at 40℃ and 75% RH for 90 days; count the number of leaking particles and calculate the oil leakage rate.

[0090] Judgment criteria: Oil spots on the surface of the capsule and oil seepage through the sealing edge are both considered leakage.

[0091] The results are shown in Table 3.

[0092] Table 3. Oil penetration rate (%) of krill oil soft capsules.

[0093]

[0094] The results showed that the oil leakage rate of the krill oil soft capsules prepared in Examples 1-3 of the present invention was 0%-4%, indicating that the film-forming composition provided by the present invention has excellent oil-blocking performance under long-term high temperature and high humidity storage, which greatly solves the problems of oil leakage and oxidation and deterioration of contents in traditional plant-based soft capsules during long-term storage.

[0095] Comparing Example 3 with Comparative Examples 1 and 2, it is evident that the lack of oat β-glucan or enzymatically hydrolyzed gluten in the film-forming composition significantly reduced the oil penetration rate of the krill oil soft capsules. This indicates that oat β-glucan and enzymatically hydrolyzed gluten can work together to block oil penetration.

[0096] Comparing Example 3 and Comparative Example 3, it can be seen that the increased content of enzymatically hydrolyzed gluten in the film-forming composition will damage the dense barrier of the membrane and exacerbate the risk of oil leakage during long-term storage.

[0097] Detection Example 4 Low-temperature storage brittleness test Take 30 krill oil soft capsules, seal them in an aluminum-plastic bag, and store them in a -10℃ freezer for 15 days. Take them out and let them warm to room temperature for 30 minutes, then gently shake them for 5 minutes. Count the number of cracked and brittle particles and calculate the brittleness rate.

[0098] The results are shown in Table 4.

[0099] Table 4. Crack rate (%) of krill oil soft capsules.

[0100]

[0101] The results showed that the brittleness rate of the krill oil soft capsules prepared in Examples 1-3 of the present invention was 0%-3%, indicating that the film-forming composition provided by the present invention has excellent shell toughness under low temperature conditions, solving the problems of easy brittleness and high damage rate of existing plant films during low temperature drying and transportation.

[0102] Comparing Example 3 with Comparative Examples 1 and 2, it is evident that the lack of oat β-glucan or enzymatically hydrolyzed gluten in the film-forming composition significantly worsened the fragility of the krill oil soft capsules. This indicates that oat β-glucan and enzymatically hydrolyzed gluten can work together to improve low-temperature toughness.

[0103] Comparing Example 3 and Comparative Example 3, it can be seen that an increase in the content of enzymatically hydrolyzed gluten in the film-forming composition leads to a decrease in low-temperature toughness.

[0104] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A film-forming composition, characterized in that, By mass fraction, it includes: 0.1%-0.3% gellan gum, 30%-38% hydroxypropyl starch, 1.0%-1.8% oat beta-glucan, 0.5%-1.2% pullulan, 20%-28% plasticizer, and the balance being water; The plasticizer is at least one of glycerol, sorbitol, maltitol, and enzymatically hydrolyzed gluten.

2. The film-forming composition according to claim 1, characterized in that, The method for preparing the enzymatically hydrolyzed gluten protein is as follows: gluten powder and water are mixed, protease is added for enzymatic hydrolysis, the hydrolysate is separated into solid and liquid components, and the clear liquid is dried. The protease is at least one of fig protease, papain, pepsin, chymotrypsin, trypsin, bromelain, Trichoderma listeri protease, Bacillus subtilis protease, Aspergillus honey protease, Aspergillus oryzae protease, and Aspergillus niger protease.

3. The film-forming composition according to claim 1, characterized in that, The amount of protease used is 0.5%-2% of the mass of wheat gluten; The enzymatic hydrolysis time is 4-8 hours.

4. The film-forming composition according to claim 1, characterized in that, The plasticizer is sorbitol and enzymatically hydrolyzed gluten.

5. The film-forming composition according to claim 1, characterized in that, By weight fraction, it includes: 0.25% gellan gum, 34% hydroxypropyl starch, 1.5% oat beta-glucan, 1% pullulan, 24% plasticizer, and the balance being water.

6. A method for preparing the film-forming composition according to any one of claims 1-5, characterized in that, Includes the following steps: (1) Add gellan gum, oat β-glucan and pullulan to the plasticizer and stir evenly to obtain a premix; (2) Add water to the premix and heat to dissolve it to obtain a sol solution; (3) Adjust the pH of the sol solution to 5.5-6.5, then add hydroxypropyl starch and homogenize.

7. The preparation method according to claim 6, characterized in that, The temperature rise mentioned in step (2) is to raise the temperature to 60-90℃; the pH adjuster mentioned in step (3) is citric acid.

8. The use of the film-forming composition according to any one of claims 1-5 or the film-forming composition prepared by the preparation method according to any one of claims 6-7 in the preparation of soft capsules.

9. A soft capsule, comprising a soft capsule shell and contents, characterized in that, The soft capsule shell is prepared from the film-forming composition according to any one of claims 1-5 or the film-forming composition prepared by the preparation method according to any one of claims 6-7.

10. A method for preparing a soft capsule, characterized in that, Includes the following steps: S1. Degas the film-forming composition according to any one of claims 1-5 or the film-forming composition prepared by the preparation method according to any one of claims 6-7 to obtain a gel. S2. Press the gel and its contents into shape to obtain the final product.

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