Rapidly disintegrated pullulan hollow capsule

Abstract

The invention relates to a rapid disintegration type pullulan hollow capsule, which belongs to the technical field of medicinal hollow capsules and comprises the following components in percentage by mass: 85 to 95 percent of pullulan, 0.01 to 5.0 percent of humectant, 0.01 to 10 percent of surfactant, 0.1 to 10 percent of gel, 0.01 to 3 percent of coagulator, 0 to 5 percent of disintegrating agent and 0.1 to 10 percent of opacifier. The preparation method comprises the following steps: dissolving at low temperature, standing and curing, forming a film at low temperature and drying at low temperature to obtain a pulullan hollow capsule shell finished product. The preparation method has the beneficial effects that a controllable loose network is formed by adopting a specific limited amount of surfactant to cooperate with the gel, a traditional plasticizer is abandoned, a specific humectant is used, and the dosage is limited; the disintegration time is shortened from 13-15 minutes to less than 9 minutes; on the premise of not using a conventional high-amount disintegrating agent, the disintegration time is shortened by more than 40%, and an unexpected technical effect is achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicinal hollow capsules, in particular to a rapid disintegration type pullulan hollow capsule. BACKGROUND

[0002] Hollow capsules are mainly used to hold powdered medicines. For example, self-made powders, health products, and medicines, which solve the problems of difficult entry and poor taste for the taker, and truly realize that good medicine is no longer bitter. Hollow capsules are becoming more and more popular, first of all, the shape of the capsule is long and slender, easy to swallow, and can effectively mask the unpleasant taste and smell of the contents, which is the most popular dosage form among patients.

[0003] The disintegration time of the existing capsule shell is generally 13-15 minutes, which is difficult to meet the demand of rapid disintegration and release of medicines. Although the pullulan capsule has the advantage of non-animal origin, the traditional pullulan capsule has the problems of slow disintegration (generally > 15 minutes) and dense film structure leading to delayed dissolution due to the entanglement of high molecular chains and ionic crosslinking.

[0004] The prior art solves the problem by adding a disintegrating agent, but it easily affects the mechanical strength of the shell. Some improve the disintegration delay problem by high-temperature drying, but it easily leads to excessive densification of the film structure. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a pullulan capsule shell with a disintegration time of less than 9 minutes and high surface finish.

[0006] To solve the above technical problems, the technical solution adopted by the present application is a rapid disintegration type pullulan hollow capsule, characterized by being composed of the following components in mass percentage: 85-95% pullulan, 0.01-5.0% humectant, 0.01-10% surfactant, 0.1%-10% gelling agent, 0.01-3% coagulant, 0-5% disintegrating agent, and 0.1-10% sunscreen.

[0007] Among them: The humectant is one or more of glycerol, polyethylene glycol, and sorbitol.

[0008] The surfactant is one or more of sodium dodecyl sulfate and polysorbate 80.

[0009] The gelling agent is one or more of carrageenan, gum arabic, gellan gum, xanthan gum, agar, and sodium alginate.

[0010] The coagulant is one or more of potassium citrate, potassium chloride, and calcium chloride.

[0011] The disintegrant is one or both of microcrystalline cellulose and hydroxypropyl cellulose.

[0012] The opacifying agent is one or several of titanium dioxide, zinc oxide, calcium carbonate, barium sulfate, and calcium phosphate.

[0013] The preparation method comprises the following steps: Step one: preparation of glue solution, low-temperature dissolution, 1000 parts of pullulan are proportioned, and each component is added into 3000-5000 parts of 40-60°C hot water for stirring and dissolution for 45-60 min, then heated to 85-90°C, and then uniformly mixed by keeping stirring for 1-2 h.

[0014] Step two: standing and ripening, placed in a heat preservation barrel and standing and ripening at a temperature of 45-65°C for 4-12 h.

[0015] Step three: low-temperature film forming, dipping in glue in an environment with a temperature of 55-55°C and a relative humidity of 40-60%.

[0016] Step four: standing and drying, standing and drying for 0.5-2 h under conditions of an oven temperature of 15-40°C and a relative humidity of 35-45%.

[0017] Step five: demolding, cutting, and fitting to obtain a pullulan hollow capsule shell product.

[0018] A preferred preparation method is as follows: Raw material mass percentage proportioning: 93% of pullulan (viscosity 50-70 mPa·s), 0.7% of sorbitol, 1.2% of polysorbate 80, 0.8% of gellan gum, 0.8% of potassium citrate, 3% of hydroxypropyl cellulose, and 0.5% of titanium dioxide.

[0019] After the raw materials are uniformly mixed, they are added into 3.7 times mass parts of 52°C purified water hot water for stirring and dissolution for 53 min, then heated to 88°C, and stirred at this temperature for 70 min, then placed in a heat preservation barrel and standing at a temperature of 55°C for 9 h. Then, dipping in glue in an environment with a temperature of 47°C and a relative humidity of 50%, then drying for 80 min under conditions of an oven temperature of 28°C and a relative humidity of 40%, and then demolding, cutting, and fitting to obtain a pullulan hollow capsule shell product. Inspection shows that the disintegration time of the hollow capsule shell body is 7.5±0.5 min, which is already completely less than 9 min.

[0020] Compared with the prior art, the present application has the following beneficial effects: (1) A specific amount of surfactant (0.01-10%) is used to form a controllable loose network with a gelation agent (0.1-10%) to create a rapid water molecule penetration channel under the premise of ensuring film strength; The traditional plasticizer (such as PEG4000) is abandoned, and a specific moisturizing agent (glycerol, etc.) is used instead, and the amount is limited (<5%), to avoid excessive delay of disintegration; The coagulant (potassium citrate, etc.) precisely controls the rheological properties of the glue solution at a low dosage of 0.01-3%; The comprehensive effect is that the disintegration time is shortened from 13-15 minutes to less than 9 minutes; Without using conventional high-dosage disintegrating agents (only 0-5%, or even no addition), the disintegration time is shortened by more than 40%, achieving unexpected technical effects.

[0021] (2) The whole process uses a low-temperature process below 90°C, combined with strict humidity control (35-45%RH), to reduce energy consumption, promote molecular chain ordering, replace traditional high-temperature crosslinking, inhibit surface hardening, and form an internal porous structure, avoiding high-temperature densification.

[0022] (3) Non-animal raw materials are used, meeting the requirements of vegetarians. DETAILED DESCRIPTION

[0023] The application will be further described below in conjunction with examples, which are intended to illustrate the application rather than further limit the protection scope of the application. EXAMPLE

[0024] The raw materials are prepared according to the following mass percentage: 90% pullulan (viscosity 50-70 mPa·s), 2% glycerol, 1.5% polysorbate 80, 1.2% carrageenan, 0.3% potassium citrate, 2% hydroxypropyl cellulose, and 3% titanium dioxide.

[0025] After the raw materials are mixed uniformly, they are added to 3.0 times the mass of 40°C purified water and stirred to dissolve for 45 minutes, then heated to 85°C and stirred at this temperature for 60 minutes, then placed in a holding barrel at a temperature of 45°C for 4 hours. Then dip the glue in an environment with a temperature of 45°C and a relative humidity of 40%, then dry it in an oven with a temperature of 15°C and a relative humidity of 35% for 30 minutes, then demold, cut, and fit to obtain the finished pullulan hollow capsule shell.

[0026] After inspection, the disintegration time of the hollow capsule shell is 7.9±0.8 minutes, which is already less than 9 minutes. EXAMPLE

[0027] The raw materials are prepared according to the following mass percentages: 95% pullulan (viscosity 50-70 mPa·s), 1% glycerol, 0.8% polysorbate 80, 0.6% carrageenan, 0.3% potassium citrate, 1% hydroxypropyl cellulose, 1.3% titanium dioxide.

[0028] After the raw materials are uniformly mixed, they are added to 4.0 times the mass of 45°C purified water and stirred to dissolve for 50 minutes, then heated to 86°C and stirred at this temperature for 50 minutes, then placed in a holding barrel and allowed to stand at a temperature of 50°C for 6 hours. Then the glue is dipped in an environment with a temperature of 50°C and a relative humidity of 45%, then dried for 60 minutes under conditions with an oven temperature of 20°C and a relative humidity of 40%, then demolded, cut, and sleeved to obtain the finished pullulan hollow capsule shell.

[0029] Upon inspection, the disintegration time of the hollow capsule shell body is 7.8±0.7 minutes, which is completely less than 9 minutes. Example

[0030] The raw materials are prepared according to the following mass percentages: 95% pullulan (viscosity 50-70 mPa·s), 1% glycerol, 0.8% polysorbate 80, 0.6% carrageenan, 0.3% potassium citrate, 1% hydroxypropyl cellulose, 1.3% titanium dioxide.

[0031] After the raw materials are uniformly mixed, they are added to 3.7 times the mass of 52°C purified water and stirred to dissolve for 53 minutes, then heated to 88°C and stirred at this temperature for 70 minutes, then placed in a holding barrel and allowed to stand at a temperature of 55°C for 9 hours. Then the glue is dipped in an environment with a temperature of 47°C and a relative humidity of 50%, then dried for 80 minutes under conditions with an oven temperature of 28°C and a relative humidity of 40%, then demolded, cut, and sleeved to obtain the finished pullulan hollow capsule shell.

[0032] Upon inspection, the disintegration time of the hollow capsule shell body is 7.5±0.5 minutes, which is completely less than 9 minutes. Example

[0033] The raw materials are prepared according to the following mass percentages: 95% pullulan (viscosity 50-70 mPa·s), 1% glycerol, 0.8% polysorbate 80, 0.6% carrageenan, 0.3% potassium citrate, 1% hydroxypropyl cellulose, 1.3% titanium dioxide.

[0034] The raw materials are mixed uniformly and then added into 5 times of mass fraction of purified water heated to 60℃ and stirred for 60 minutes, then heated to 90℃ and stirred for 120 minutes at this temperature, then placed in a heat preservation barrel at a temperature of 65℃ for 12 hours. Then dip the glue in an environment with a temperature of 55℃ and a relative humidity of 60%, and then dry for 120 minutes under the conditions of an oven temperature of 40℃ and a relative humidity of 45%, and then perform demolding, cutting and sleeving to obtain the finished product of the pullulan hollow capsule shell.

[0035] Through inspection, the disintegration time of the hollow capsule shell body is 8.0±0.7 minutes, which is completely less than 9 minutes. Example

[0036] The raw materials are mixed uniformly and then added into 5 times of mass fraction of purified water heated to 60℃ and stirred for 60 minutes, then heated to 90℃ and stirred for 120 minutes at this temperature, then placed in a heat preservation barrel at a temperature of 65℃ for 12 hours. Then dip the glue in an environment with a temperature of 55℃ and a relative humidity of 60%, and then dry for 120 minutes under the conditions of an oven temperature of 40℃ and a relative humidity of 45%, and then perform demolding, cutting and sleeving to obtain the finished product of the pullulan hollow capsule shell.

[0037] The raw materials are mixed uniformly and then added into 5 times of mass fraction of purified water heated to 60℃ and stirred for 60 minutes, then heated to 90℃ and stirred for 120 minutes at this temperature, then placed in a heat preservation barrel at a temperature of 65℃ for 12 hours. Then dip the glue in an environment with a temperature of 55℃ and a relative humidity of 60%, and then dry for 120 minutes under the conditions of an oven temperature of 40℃ and a relative humidity of 45%, and then perform demolding, cutting and sleeving to obtain the finished product of the pullulan hollow capsule shell.

[0038] Through inspection, the disintegration time of the hollow capsule shell body is 8.1±0.6 minutes, which is completely less than 9 minutes.

[0039] The disintegration test is performed on the capsule shell bodies prepared in Examples 1-5.

[0040] 100 pullulan hollow capsules produced in each example are randomly selected for testing, filled with talcum powder as the content, and then respectively placed in simulated gastric juice with a temperature of (37±1)℃ and pH=1.1 and simulated intestinal juice with pH=7.9 to measure the disintegration time, and record the average time required for the capsules of the products of each example to start disintegrating and completely disintegrating.

[0041] Table 1: Detection results of the disintegration time of pullulan hollow capsules

[0042]

[0043] As shown in Table 1, the hollow capsules produced in each example of the present application have a disintegration time limit in simulated gastric juice of more than 2 hours, a starting disintegration time limit in simulated intestinal juice of between 3.2-4.4 minutes, and a complete disintegration time limit of between 7.0-8.7 minutes, effectively shortening the disintegration time; and the solvent residue is very little or even none.

Claims

1. A fast disintegrating pullulan polysaccharide hollow capsule, characterized in that The invention is composed of the following components in the following mass percentages: 85-95% pullulan, 0.01-5.0% moisturizer, 0.01-10% surfactant, 0.1%-10% gelling agent, 0.01-3% coagulant, 0-5% disintegrant, and 0.1-10% sunscreen.

2. The fast-disintegrating pullulan empty capsule according to claim 1, characterized in that The preparation method comprises the following steps: Step 1: Dissolve at low temperature. Add 3000-5000 parts of 40-60℃ hot water to 1000 parts of pullulan and stir to dissolve for 45-60 minutes. Then heat to 85-90℃ and keep stirring for 1-2 hours to mix evenly. Step 2: Place in a heat preservation barrel at 45-65℃ for 4-12 hours; Step 3: Low temperature film formation, dipping in glue at a temperature of 45-55°C and a relative humidity of 40-60%; Step 4: Place it aside to dry for 0.5-2 hours at a drying oven temperature of 15-40°C and a relative humidity of 35-45%. Step 5: demoulding, cutting, and fitting to obtain the finished pullulan hollow capsule shell.

3. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The preparation method is as follows: ⑴Raw materials mass percentage ratio: 93% pullulan, 0.7% sorbitol, 1.2% polysorbate 80, 0.8% gellan gum, 0.8% potassium citrate, 3% hydroxypropyl cellulose, 0.5% titanium dioxide; (2) After the raw materials are evenly mixed, add them to 3.7 parts by weight of purified water at 52°C and stir to dissolve for 53 minutes. Then heat to 88°C and stir at this temperature for 70 minutes. Then place in an insulated barrel at 55°C and let stand for 9 hours. Then dip in glue at a temperature of 47°C and a relative humidity of 50%, and then dry for 80 minutes at a drying oven temperature of 28°C and a relative humidity of 40%. Then demold, cut, and fit together to obtain the finished pullulan hollow capsule shell.

4. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The moisturizing agent is one or more of glycerin, polyethylene glycol and sorbitol.

5. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The surfactant is one or more of sodium lauryl sulfate and polysorbate 80.

6. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The gelling agent is one or more of carrageenan, gum arabic, gellan gum, xanthan gum, agar, and sodium alginate.

7. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The coagulant is one or more of potassium citrate, potassium chloride and calcium chloride.

8. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The disintegrant is one or both of microcrystalline cellulose and hydroxypropyl cellulose.

9. The fast-disintegrating pullulan empty capsule according to claim 2, characterized in that The sunscreen is one or more of titanium dioxide, zinc oxide, calcium carbonate, barium sulfate and calcium phosphate.

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