CN116919915B - Double-layer soft capsule, preparation method and application - Google Patents
Double-layer soft capsule, preparation method and application Download PDFInfo
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- CN116919915B CN116919915B CN202310917616.4A CN202310917616A CN116919915B CN 116919915 B CN116919915 B CN 116919915B CN 202310917616 A CN202310917616 A CN 202310917616A CN 116919915 B CN116919915 B CN 116919915B
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- 239000007901 soft capsule Substances 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 229920001218 Pullulan Polymers 0.000 claims abstract description 57
- 239000004373 Pullulan Substances 0.000 claims abstract description 57
- 235000019423 pullulan Nutrition 0.000 claims abstract description 57
- 239000000679 carrageenan Substances 0.000 claims abstract description 42
- 229920001525 carrageenan Polymers 0.000 claims abstract description 42
- 235000010418 carrageenan Nutrition 0.000 claims abstract description 42
- 229940113118 carrageenan Drugs 0.000 claims abstract description 42
- 239000002994 raw material Substances 0.000 claims abstract description 42
- 239000006187 pill Substances 0.000 claims abstract description 38
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000001035 drying Methods 0.000 claims abstract description 27
- 238000003825 pressing Methods 0.000 claims abstract description 26
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims abstract description 26
- 229920002472 Starch Polymers 0.000 claims abstract description 23
- 239000008107 starch Substances 0.000 claims abstract description 23
- 235000019698 starch Nutrition 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000012153 distilled water Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 238000005498 polishing Methods 0.000 claims abstract description 18
- 238000007493 shaping process Methods 0.000 claims abstract description 18
- -1 carrageenan oligosaccharide Chemical class 0.000 claims abstract description 16
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 16
- RQFQJYYMBWVMQG-IXDPLRRUSA-N chitotriose Chemical compound O[C@@H]1[C@@H](N)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](N)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)[C@@H](CO)O1 RQFQJYYMBWVMQG-IXDPLRRUSA-N 0.000 claims abstract description 14
- 239000011248 coating agent Substances 0.000 claims abstract description 13
- 238000000576 coating method Methods 0.000 claims abstract description 13
- 239000001103 potassium chloride Substances 0.000 claims abstract description 10
- 239000003292 glue Substances 0.000 claims description 68
- 238000010438 heat treatment Methods 0.000 claims description 28
- 238000002844 melting Methods 0.000 claims description 16
- 230000008018 melting Effects 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- 239000004744 fabric Substances 0.000 claims description 8
- 238000003892 spreading Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 230000008014 freezing Effects 0.000 abstract description 4
- 238000007710 freezing Methods 0.000 abstract description 4
- 238000005057 refrigeration Methods 0.000 abstract description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 abstract description 2
- 238000005336 cracking Methods 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 description 14
- 241000196324 Embryophyta Species 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 5
- 150000004676 glycans Chemical class 0.000 description 5
- 229920001282 polysaccharide Polymers 0.000 description 5
- 239000005017 polysaccharide Substances 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 241001474374 Blennius Species 0.000 description 2
- 241001391944 Commicarpus scandens Species 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241001633942 Dais Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
The invention provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein, the preparation raw materials of the inner layer comprise: pullulan I, carrageenan oligosaccharide, carrageenan, starch and distilled water; the preparation raw materials of the outer layer comprise: pullulan II, KCl, carrageenan, glycerol, chitosan oligosaccharide and distilled water. The technical scheme is based on the soft capsule process, the double-layer rubber is formed by coating the outer layer on the inner layer rubber before forming, then the double-layer rubber is pressed into soft capsules by a soft capsule pill pressing machine, and finally, the double-layer soft capsule product is obtained through shaping, polishing, drying and pill selection; the soft capsule prepared by the invention can be stored for a long time under the conditions of refrigeration and freezing, and the phenomena of cracking, leakage and the like can not occur.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a double-layer soft capsule, a preparation method and application.
Background
The soft capsule is a capsule prepared by directly sealing a certain amount of liquid materials or dissolving or dispersing solid materials in proper auxiliary materials to prepare solution, suspension, emulsion or semisolid, and sealing the soft capsule materials. The main advantages are that the bad smell of the medicine can be covered, and the irritation is reduced; high bioavailability, rapid dispersion and good absorption; the stability is good, and the influence of water, oxygen and illumination in the air can be avoided; no adhesive or the like is required to be added. However, when the existing soft capsules are filled with water-soluble solid raw materials, the water-soluble solid raw materials are prepared into suspension by auxiliary materials, so that poor uniformity is easily caused; in addition, when the gastric or enteric soft capsules are produced, the additional coating is needed, so that the process is more complex.
Gelatin capsules suffer from a number of drawbacks: (1) The gelatin hollow capsule is easy to generate cross-linking reaction to influence the release of the medicine; (2) The gelatin hollow capsule has some potential safety hazards, such as the risk of virus carrying in the gelatin hollow capsule raw material caused by frequent outbreaks of animal epidemic situation. The plant capsule has no protein toxin of animal gelatin, no preservative, no need of ethylene oxide sterilization, and thus has the advantages of high safety, stable chemical property, no crosslinking reaction and the like. At present, the main raw materials of the novel plant polysaccharide comprise cellulose, plant polysaccharide and plant starch.
CN102579391a provides a gastric soluble compound seaweed polysaccharide film coating premix and a liquid preparation method thereof. The raw materials comprise seaweed polysaccharide gum, plant dietary fiber, plasticizer and other auxiliary components. The main raw material used in the invention is natural polymer material-seaweed polysaccharide gum with safety and low cost, the obtained coating has good application performance, and various indexes after being coated accord with the regulations of the current edition of the pharmacopoeia of the people's republic of China.
CN106943375a discloses a plant capsule and a preparation method thereof, and the plant capsule is prepared by glue preparation, glue dipping and drying, and has the characteristics of simple process route, short production period, low energy consumption, low cost and easy molding, and the prepared plant capsule product has good toughness, is not easy to break, and retains the original natural golden and silvery white colors of plants.
The existing capsules are easy to break after being stored under refrigeration or freezing conditions for a long time, and the prepared coating can be wrinkled and the like in order to realize enteric or gastric dissolution conditions. Aiming at the phenomenon, the invention provides a double-layer soft capsule, a preparation method and application.
Disclosure of Invention
The invention aims to provide a double-layer soft capsule which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: pullulan I, carrageenan oligosaccharide, carrageenan, starch and distilled water;
the preparation raw materials of the outer layer comprise: pullulan II, KCl, carrageenan, glycerol, chitosan oligosaccharide and distilled water.
Preferably, the carrageenan oligosaccharides have a molecular weight of (1-2) kDa.
Preferably, the carrageenan oligosaccharides have a molecular weight of 1.4kDa.
Preferably, the inner layer is prepared from the following raw materials in percentage by weight: 0.1-15% of pullulan I, 0.1-5% of carrageenan oligosaccharide, 1-8% of carrageenan, 1.5-5.5% of starch and the balance of distilled water.
Preferably, the preparation raw materials of the outer layer comprise the following components in percentage by weight: 6-20% of pullulan II, 0.05-1.5% of KCl, 1-4% of carrageenan, 0.01-1% of glycerol, 0.5-2.0% of chitosan oligosaccharide and the balance of distilled water.
Preferably, the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a weight average molecular weight of about 20W.
Preferably, the pullulan ii has a weight average molecular weight of about 20W.
In another aspect, the present invention provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing the raw materials, heating, stirring and melting at 70-80deg.C;
2) Preparing an outer layer glue solution: mixing the raw materials, heating, stirring and melting at 70-80deg.C;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Preferably, the condition of the step 4) is that the temperature is 18-26 ℃, the humidity is 25-40% and the time is 2-4 hours; the condition of the step 5) is that the drying temperature is 20-30 ℃ and the humidity is 20-35%.
The invention also provides the double-layer soft capsule which is applied to the field of medicine requiring refrigeration and freezing preservation.
By adopting the technical scheme, the invention has the following beneficial effects:
1. the technical scheme is based on the soft capsule process, the double-layer rubber is formed by coating the outer layer on the inner layer rubber before forming, then the double-layer rubber is pressed into soft capsules by a soft capsule pill pressing machine, and finally, the double-layer soft capsule product is obtained through shaping, polishing, drying and pill selection;
2. the soft capsule prepared by the invention can be stored for a long time under the conditions of refrigeration and freezing, and the phenomena of cracking, leakage and the like can not occur.
Detailed Description
The following description of the present invention will be made clearly and fully, and it is apparent that the embodiments described are some, but not all, of the embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In the invention, the mass ratio of the inner layer glue solution to the outer layer glue solution used in preparation can be adjusted according to actual needs, and the ratio used in the embodiment is 1:2, to give an example.
Example 1
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: 8% of pullulan I, 2% of carrageenan oligosaccharide, 8% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the weight average molecular weight was 1.83×10 5 Pullulan of DaIs prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol, 1.2% of chitosan oligosaccharide and the balance of distilled water.
Pullulan having a weight average molecular weight of 20W is commercially available, and carrageenan oligosaccharides are iota-type (1.4 kDa) and purchased from the peninsula Bozhi Hui biotechnology Co. Carrageenan is purchased from the company of the biological technology of the sea in the Lian Yungang, and the model is KA120; the starch is pea starch. Chitosan oligosaccharide was purchased from Qingdao and Marine biotechnology Co., ltd under the trade designation:the molecular weight is not more than 1500Da.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Example 2
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
raw materials for preparing inner layerComprising the following steps: 8% of pullulan I, 8% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the weight average molecular weight was 1.83×10 5 The preparation of pullulan of Da was prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol, 1.2% of chitosan oligosaccharide and the balance of distilled water.
Pullulan with a weight average molecular weight of 20W is commercially available, and carrageenan is purchased from Liyun Kong Tianhai biotechnology Co., ltd, model KA120; the starch is pea starch. Chitosan oligosaccharide was purchased from Qingdao and Marine biotechnology Co., ltd under the trade designation:the molecular weight is not more than 1500Da.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Example 3
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: 8% of pullulan I, 2% of carrageenan oligosaccharide, 8% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the weight average molecular weight was 1.83×10 5 The preparation of pullulan of Da was prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol and the balance of distilled water.
Pullulan having a weight average molecular weight of 20W is commercially available, and carrageenan oligosaccharides are iota-type (1.4 kDa) and purchased from the peninsula Bozhi Hui biotechnology Co. Carrageenan is purchased from the company of the biological technology of the sea in the Lian Yungang, and the model is KA120; the starch is pea starch.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Example 4
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: 8% of pullulan I, 2% of carrageenan oligosaccharide, 8% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I is pullulan with a weight average molecular weight of about 20W;
the weight average molecular weight was 1.83×10 5 The preparation of pullulan of Da was prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol, 1.2% of chitosan oligosaccharide and the balance of distilled water.
Pullulan having a weight average molecular weight of 20W is commercially available, and carrageenan oligosaccharides are iota-type (1.4 kDa) and purchased from the peninsula Bozhi Hui biotechnology Co. Carrageenan is purchased from the company of the biological technology of the sea in the Lian Yungang, and the model is KA120; the starch is pea starch. Chitosan oligosaccharide was purchased from Qingdao and Marine biotechnology Co., ltd under the trade designation:the molecular weight is not more than 1500Da.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Example 5
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: pullulan I8%, chitosan oligosaccharide 2%, carrageenan 8%, starch 2.5% and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the weight average molecular weight was 1.83×10 5 The preparation of pullulan of Da was prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol, 1.2% of carrageenan oligosaccharide and the balance of distilled water.
Pullulan having a weight average molecular weight of 20W is commercially available, and carrageenan oligosaccharides are iota-type (1.4 kDa) and purchased from the peninsula Bozhi Hui biotechnology Co. Carrageenan is purchased from the company of the biological technology of the sea in the Lian Yungang, and the model is KA120; the starch is pea starch. Chitosan oligosaccharide was purchased from Qingdao and Marine biotechnology Co., ltd under the trade designation:the molecular weight is not more than 1500Da.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Example 6
The embodiment provides a double-layer soft capsule, which comprises an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: 9% of pullulan I, 4% of carrageenan oligosaccharide, 6% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the weight average molecular weight was 1.83×10 5 The preparation of pullulan of Da was prepared by the method of example 2 in patent CN 112760231B;
the preparation raw materials of the outer layer comprise: 15% of pullulan II, 0.09% of KCl, 4% of carrageenan, 0.4% of glycerol, 1.6% of chitosan oligosaccharide and the balance of distilled water.
Pullulan having a weight average molecular weight of 20W is commercially available, and carrageenan oligosaccharides are iota-type (1.4 kDa) and purchased from the peninsula Bozhi Hui biotechnology Co. Carrageenan is purchased from the company of the biological technology of the sea in the Lian Yungang, and the model is KA120; the starch is pea starch. Chitosan oligosaccharide was purchased from Qingdao and Marine biotechnology Co., ltd under the trade designation:the molecular weight is not more than 1500Da.
Another aspect of this embodiment provides a method for preparing the double-layer soft capsule, which comprises the following steps:
1) Preparing an inner layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
2) Preparing an outer layer glue solution: mixing, heating, stirring and melting the raw materials, wherein the heating temperature is 75+/-3 ℃;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage; the temperature is 20+/-2 ℃ and the humidity is 30+/-2%;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth; the drying temperature is 25+/-2 ℃ and the humidity is 30+/-5%;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
Performance test:
1. appearance property observation: from the phenomena of smooth appearance, uniform color, special-shaped pills, bubble pills, loopholes and the like.
2. Rubber strength (F) and toughness index (T): adopting a physical property tester, selecting a spherical probe and a puncture mode, and recording the breaking force of the rubber at the test speed of 1.0mm/s, wherein the higher the breaking force is, the better the strength of the rubber is; the larger the breaking distance is, the better the toughness of the rubber is.
3. Crack adhesion index: cutting the capsule on the non-slit, extruding and emptying the content, then cutting a ring containing two slits from the middle perpendicularly to the slits, placing the ring on a glass slide, perpendicularly arranging the two slits on the glass slide, measuring the thickness of the two slits and the thickness of the capsule shell under a microscope, and calculating the ratio P (%) of the thickness of the thinnest slit to the thickness of the capsule shell.
Table 1 criteria for evaluating the strength, toughness and crack adhesion index of soft capsule skin
4. And (3) detecting disintegration time limit: with reference to the specification of the disintegration time period in the united states pharmacopeia USP <2040>, the soft capsule was subjected to a disintegration test in a simulated intestinal fluid using a basket apparatus, and the acceptable disintegration is represented by the symbol "v" within 60 minutes, wherein the very acceptable disintegration is represented by the symbol "v", the unacceptable disintegration is represented by the symbol "x", and the almost unacceptable disintegration is represented by the symbol "v x". Very conforming means disintegrating in the first 20 minutes, hardly conforming means disintegrating in the last 20 minutes.
TABLE 2 test results for test 1-4
Performance test 5: the capsules prepared in examples 1 to 6 were stored in a refrigerating chamber at 0℃for 15d and were left outdoors (25 ℃) for 5min each day, followed by the above-mentioned tests 2 to 4, and the results were tested as follows. And simultaneously placing the dried cotton in the capsule, and shearing after testing to check whether the cotton is wet or not.
TABLE 3 test results for test 5
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (3)
1. A double-layer soft capsule is characterized by comprising an inner layer and an outer layer; wherein,
the preparation raw materials of the inner layer comprise: 8% of pullulan I, 2% of carrageenan oligosaccharide, 8% of carrageenan, 2.5% of starch and the balance of distilled water; the pullulan I has a weight average molecular weight of 1.83×10 5 A mixture of pullulan of Da and pullulan having a molecular weight of about 20W in a mass ratio of 1:10;
the preparation raw materials of the outer layer comprise: 10% of pullulan II, 0.08% of KCl, 2% of carrageenan, 0.4% of glycerol, 1.2% of chitosan oligosaccharide and the balance of distilled water; the weight average molecular weight of the pullulan II is about 20W.
2. A method for preparing the double-layer soft capsule of claim 1, characterized by the steps of:
1) Preparing an inner layer glue solution: mixing the raw materials, heating, stirring and melting at 70-80deg.C;
2) Preparing an outer layer glue solution: mixing the raw materials, heating, stirring and melting at 70-80deg.C;
3) And (3) pelleting: spreading the inner glue solution into a glue sheet on a pill pressing machine, coating the outer glue solution on the outer surface of the inner glue sheet to form a double-layer glue sheet, and pressing the double-layer glue sheet and the content into soft capsules by a soft capsule pill pressing machine;
4) Shaping: shaping the pressed soft capsule in a rotating cage;
5) Polishing and drying: polishing and drying the shaped soft capsules in a rotating cage by using pill wiping cloth;
6) Pill selection: and removing unqualified soft capsules from the dried soft capsules to obtain qualified soft capsule products.
3. The method according to claim 2, wherein the conditions of step 4) are a temperature of 18-26 ℃, a humidity of 25-40% and a time of 2-4 hours; the condition of the step 5) is that the drying temperature is 20-30 ℃ and the humidity is 20-35%.
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| WO2001060340A1 (en) * | 2000-02-16 | 2001-08-23 | Bioprogress Technology International Inc. | Delivery capsules |
| JP2007320875A (en) * | 2006-05-31 | 2007-12-13 | Sansho Pharmaceutical Co Ltd | Capsule |
| CN102670563A (en) * | 2012-06-05 | 2012-09-19 | 江南大学 | Preparation method of soft capsule without gelatin |
| CN114306273A (en) * | 2022-01-11 | 2022-04-12 | 新昌辽远科技有限公司 | Multilayer hollow capsule and preparation method thereof |
| CN114699381A (en) * | 2022-03-09 | 2022-07-05 | 江苏力凡胶囊有限公司 | Pullulan polysaccharide plant soft capsule and preparation method thereof |
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| WO2001060340A1 (en) * | 2000-02-16 | 2001-08-23 | Bioprogress Technology International Inc. | Delivery capsules |
| JP2007320875A (en) * | 2006-05-31 | 2007-12-13 | Sansho Pharmaceutical Co Ltd | Capsule |
| CN102670563A (en) * | 2012-06-05 | 2012-09-19 | 江南大学 | Preparation method of soft capsule without gelatin |
| CN114306273A (en) * | 2022-01-11 | 2022-04-12 | 新昌辽远科技有限公司 | Multilayer hollow capsule and preparation method thereof |
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