CN114767652B - Polycarbofil calcium dry suspension and preparation method and application thereof - Google Patents
Polycarbofil calcium dry suspension and preparation method and application thereof Download PDFInfo
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- CN114767652B CN114767652B CN202210431862.4A CN202210431862A CN114767652B CN 114767652 B CN114767652 B CN 114767652B CN 202210431862 A CN202210431862 A CN 202210431862A CN 114767652 B CN114767652 B CN 114767652B
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- 239000000725 suspension Substances 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000011575 calcium Substances 0.000 title description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title description 3
- 229910052791 calcium Inorganic materials 0.000 title description 3
- 229920000148 Polycarbophil calcium Polymers 0.000 claims abstract description 76
- 239000002245 particle Substances 0.000 claims abstract description 67
- 229950005134 polycarbophil Drugs 0.000 claims abstract description 64
- 239000002994 raw material Substances 0.000 claims abstract description 40
- 229920001503 Glucan Polymers 0.000 claims abstract description 24
- 239000000796 flavoring agent Substances 0.000 claims abstract description 18
- 239000003085 diluting agent Substances 0.000 claims abstract description 17
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 12
- 229940059101 polycarbophil calcium Drugs 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims description 45
- 238000002156 mixing Methods 0.000 claims description 22
- 229920002307 Dextran Polymers 0.000 claims description 17
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 9
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 8
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 7
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- 235000019634 flavors Nutrition 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 4
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 4
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
- 239000008267 milk Substances 0.000 claims description 3
- 235000013336 milk Nutrition 0.000 claims description 3
- 210000004080 milk Anatomy 0.000 claims description 3
- 239000007958 cherry flavor Substances 0.000 claims description 2
- 239000007968 orange flavor Substances 0.000 claims description 2
- 240000008790 Musa x paradisiaca Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000006068 taste-masking agent Substances 0.000 claims 1
- 239000008371 vanilla flavor Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 29
- 230000000694 effects Effects 0.000 abstract description 8
- 230000036571 hydration Effects 0.000 abstract description 5
- 238000006703 hydration reaction Methods 0.000 abstract description 5
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 230000007935 neutral effect Effects 0.000 abstract description 4
- 239000007909 solid dosage form Substances 0.000 abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 238000010521 absorption reaction Methods 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 8
- 241000234295 Musa Species 0.000 description 7
- 238000004062 sedimentation Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 239000000375 suspending agent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000011812 mixed powder Substances 0.000 description 5
- 235000013339 cereals Nutrition 0.000 description 4
- 239000008119 colloidal silica Substances 0.000 description 4
- 210000003608 fece Anatomy 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 235000005976 Citrus sinensis Nutrition 0.000 description 3
- 240000002319 Citrus sinensis Species 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 208000019505 Deglutition disease Diseases 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 229940095498 calcium polycarbophil Drugs 0.000 description 3
- 229960001681 croscarmellose sodium Drugs 0.000 description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
- 230000013872 defecation Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 244000290333 Vanilla fragrans Species 0.000 description 2
- 235000009499 Vanilla fragrans Nutrition 0.000 description 2
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 244000307700 Fragaria vesca Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- KUQWZSZYIQGTHT-UHFFFAOYSA-N hexa-1,5-diene-3,4-diol Chemical compound C=CC(O)C(O)C=C KUQWZSZYIQGTHT-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000013441 quality evaluation Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000020985 whole grains Nutrition 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
- A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a polycarbophil dry suspension and a preparation method and application thereof. The dry suspension comprises, by weight, 30% -60% of polycarbophil calcium, 20% -50% of glucan, 5% -30% of a diluent, 1% -10% of a flavoring agent and 0-3% of a glidant. According to the invention, the polycarbophil raw material and the glucan are mixed and then crushed together, so that the glucan is wrapped on the surface of the raw material particles, and then a hydration film can be formed around the raw material particles, so that the stability of the suspension is improved, the viscosity of the solution is increased, the stability of the suspension is further improved, the taste is effectively improved, the compliance is improved, and more importantly, the complete decalcification of the raw material under an acidic condition is facilitated, and then the water is fully absorbed and expanded under a neutral condition, so that the dry suspension can exert the curative effect to the greatest extent and is superior to other solid dosage forms.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a polycarbophil dry suspension and a preparation method and application thereof.
Background
Polycarbophil is a hygroscopic yellowish white powder with a melting point of 510 ℃ and is practically insoluble in water or ethanol. The chemical name of the polycarbophil is 3, 4-dihydroxy-1, 5-hexadiene crosslinked calcium polyacrylate, the molecular formula is (C 3H3O2)a·(C6H10O2)b. Ca, molecular weight 238.20, structural formula is:
Polycarbophil is a therapeutic agent for irritable bowel syndrome, and rapidly decalcifies under acidic conditions (e.g., stomach) to form polycarbophil, which has high water absorption and water retention properties under neutral conditions (e.g., small and large intestines), and swells and gels after absorbing water. Therefore, when diarrhea occurs, the polycarbophil absorbs water in the digestive tract to gel, so that the passing time of the content is prolonged, the defecation times are reduced, the absorption of moisture in the feces is promoted, and the property of the feces is improved; on the other hand, in constipation, since polycarbophil swells by absorbing water in the digestive tract, the defecation time is shortened by softening the content or increasing its volume, the number of times of defecation is increased, while by retaining water, the decrease in water in feces is suppressed and the feces properties are improved.
The existing calcium polycarbophil preparations on the market comprise tablets, capsules, chewable tablets and granules, wherein the tablets and the capsules are not suitable for patients with dysphagia to take, and if the tablets are not disintegrated in the stomach in time, calcium polycarbophil is not completely decalcified, so that the curative effect is affected; the polycarbophil granule is dispersed before being taken, is extremely easy to sink, has gritty feel when being taken, and the chewable tablet also has gritty feel after being chewed in the mouth, so that the patient compliance is poor. Thus, there is a need to provide a new calcium polycarbophil formulation for treating diarrhea or constipation.
Disclosure of Invention
In view of the above, the primary objective of the present invention is to provide a polycarbophil dry suspension to solve the problem of poor compliance of the existing dosage forms. The dry suspension is powder or granule prepared from insoluble medicine and proper adjuvant, and can be dispersed into suspension for oral administration by shaking with water. After the dry suspension is added with water for dispersion, the particles are uniformly dispersed, the sedimentation is slow, and after the sedimentation, the particles can be redispersed by gentle shaking. The dry suspension has the characteristics of solid preparation, is convenient to carry and transport, has good stability, has the advantages of liquid preparation, is convenient to take, and is suitable for patients with dysphagia.
The invention also aims to provide a preparation method of the polycarbophil dry suspension, which can improve the stability of the suspension, effectively improve the gravel-shaped mouthfeel, is more convenient and smooth to take and has high patient compliance.
The invention aims at realizing the following technical scheme:
on one hand, the invention provides a polycarbophil dry suspension, which comprises the following raw materials in percentage by mass:
Optionally, the polycarbophil dry suspension comprises the following raw materials:
optionally, the particle size of the polycarbophil is less than 100 μm and the particle size of the dextran is less than 80 μm.
Optionally, the particle size of the polycarbophil is 10-50 μm, and the particle size of the dextran is 10-50 μm.
Optionally, the diluent is one or more of lactose, microcrystalline cellulose, sucrose, mannitol, sorbitol, erythritol.
Optionally, the flavoring agent is one or more of sweet orange essence, vanilla essence, strawberry essence, milk essence, banana essence and cherry essence.
Optionally, the glidant is one or more of colloidal silicon dioxide, talcum powder and magnesium stearate.
In another aspect, the invention provides a method for preparing the polycarbophil dry suspension, which comprises the following steps:
Crushing polycarbophil to a particle size of less than 100 mu m, adding glucan, mixing to form a first mixture, and crushing the first mixture to a particle size of less than 80 mu m to obtain a second mixture;
Finishing the diluent, and then mixing the diluent with the second mixture to form a third mixture;
respectively carrying out granule finishing treatment on the flavoring agent and the glidant, and then mixing with the third mixture to form a fourth mixture;
Subpackaging the fourth mixture.
Optionally, the polycarbophil is crushed to a particle size of less than 80 mu m and then mixed with dextran to form a first mixture, and the first mixture is crushed to a particle size of 10-50 mu m to obtain a second mixture.
Optionally, the sized flavoring agent and glidant are mixed with the third mixture in equal increments.
Optionally, the particle size of the diluent after the particle size adjustment is less than 300 μm, the particle size of the flavoring agent after the particle size adjustment is less than 250 μm, and the particle size of the glidant after the particle size adjustment is less than 250 μm.
In a third aspect, the invention also provides an application of the polycarbophil dry suspension or the polycarbophil dry suspension prepared by the method in preparation of the drug for treating irritable bowel syndrome.
Compared with the prior art, the technical scheme of the invention has the following advantages:
1. The invention provides a polycarbophil dry suspension, which comprises the following raw materials in parts by weight: 30-60% of polycarbophil, 20-50% of glucan, 5-30% of diluent, 1-10% of flavoring agent and 0-3% of glidant. Because the polycarbophil raw material is insoluble in water, the surface of the raw material particles is hydrophobic in suspension, so that the surface hydration of the particles is weak, the raw material particles are easy to gather and settle, and the glucan has high water solubility and high viscosity, just plays the roles of a wetting agent and a suspending agent, so that hydration films are formed around the polycarbophil raw material particles wrapped by the glucan, the mutual coalescence among the raw material particles can be prevented, the stability of the suspending agent is improved, the viscosity of a solution is increased by the glucan, the density difference between the particles and a medium is reduced, the stability of the suspending agent is further improved, the taste is effectively improved, and the compliance is improved.
2. The polycarbophil dry suspension provided by the invention increases the specific surface area by reducing the particle size of the polycarbophil raw material (the particle size of the untreated raw material is about 200 mu m), so that the raw material can be uniformly dispersed in the suspension and fully contacted with a medium, the sedimentation speed can be obviously reduced, the stability of the suspension can be improved, the gravel-shaped taste can be effectively improved, the taking is more convenient and smooth, and more importantly, the complete decalcification of the raw material is facilitated under an acidic condition, and the water absorption capacity is improved after the raw material is fully absorbed by water under a neutral condition, so that the polycarbophil dry suspension can exert the curative effect to the greatest extent and is superior to other solid dosage forms.
3. According to the preparation method of the polycarbophil dry suspension, the polycarbophil raw material and the glucan are mixed and crushed together, so that the glucan is coated on the surfaces of the polycarbophil particles, the glucan has high water solubility and high viscosity, the effect of a wetting agent and a suspending agent is just exerted, a hydration film is formed around the raw material particles coated by the glucan, the mutual aggregation among the raw material particles is prevented, and the stability of the suspension is improved. Meanwhile, the dextran also increases the viscosity of the solution, reduces the density difference between the particles and the medium, and further improves the stability of the suspension.
Detailed Description
The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.
The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.
The polycarbophil dry suspension provided by the embodiment of the invention comprises the following raw materials in percentage by mass:
optionally, the particle size of the polycarbophil is less than 100 μm and the particle size of the dextran is less than 80 μm. Further, the particle size of the polycarbophil is 10-50 mu m, and the particle size of the dextran is 10-50 mu m.
The invention can obviously reduce sedimentation velocity and improve stability of suspension by reducing particle size of the polycarbophil raw material (the particle size of the untreated raw material is about 200 mu m), and can effectively improve gravel-shaped mouthfeel, and the invention is more convenient and smooth to take, has high patient compliance, and more importantly, is helpful for complete decalcification of the raw material under an acidic condition, and then fully absorbs water and expands under a neutral condition to improve water absorption capacity, so that the polycarbophil dry suspension can exert curative effect to the greatest extent and is superior to other solid dosage forms.
Optionally, the diluent is one or more of lactose, microcrystalline cellulose, sucrose, mannitol, sorbitol, erythritol.
Optionally, the flavoring agent is one or more of sweet orange essence, vanilla essence, strawberry essence, milk essence, banana essence and cherry essence.
Optionally, the glidant is one or more of colloidal silicon dioxide, talcum powder and magnesium stearate.
On the other hand, the embodiment of the invention also provides a method for preparing the polycarbophil dry suspension, which comprises the following steps:
1. Pretreatment of raw materials
Firstly, crushing and grinding a polycarbophil raw material by using grinding balls with larger diameters, wherein the diameters of the grinding balls are more than 6mm, preferably 8mm, adding glucan to mix uniformly after the diameters of the polycarbophil raw material reach below 100 mu m, preferably below 80 mu m, replacing grinding balls with smaller diameters to crush and grind again, the diameters of the grinding balls are less than 5mm, preferably 3mm, finishing grinding when the diameters of the mixture reach 10-50 mu m, and taking out mixed powder for standby;
2. Mixing
Finishing the diluent to make the particle size smaller than 300 mu m, and then uniformly mixing the diluent with the mixed powder in the step to form a third mixture;
Finishing the grain size of the flavoring agent to be less than 250 mu m, finishing the grain size of the glidant to be less than 250 mu m, and then carrying out equal incremental mixing with the third mixture to form a fourth mixture;
3. Sub-packaging
And (5) sub-packaging the fourth mixture by a sub-packaging machine.
According to the preparation method of the polycarbophil dry suspension, the polycarbophil raw material and the glucan are mixed and crushed together, so that the glucan is coated on the surfaces of the polycarbophil particles, the glucan has high water solubility and high viscosity, the functions of a wetting agent and a suspending agent are just exerted, a hydration film is formed around the raw material particles coated by the glucan, the mutual aggregation among the raw material particles is prevented, and the stability of the suspension is improved. Meanwhile, the dextran also increases the viscosity of the solution, reduces the density difference between the particles and the medium, and further improves the stability of the suspension, thereby reducing the generation of gravel, effectively improving the taste and improving the compliance.
Example 1
Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Mannitol (mannitol) | 125g |
| Dextran | 312.5g |
| Banana flavor essence | 50g |
| Colloidal silica | 12.5g |
Preparing batches: 1 ten thousand bags.
The process comprises the following steps:
1. Pretreatment of raw materials
Grinding the prescription quantity of polycarbophil raw material (with the particle size of 200 mu m) by using a ball mill to prepare grinding balls with the diameter of 8mm until the particle size of the polycarbophil raw material is smaller than 80 mu m, adding glucan to mix uniformly, replacing grinding balls with the diameter of 3mm to grind, ending grinding when the particle size of the mixture reaches 10-50 mu m, and taking out mixed powder for standby;
2. Mixing
Finishing mannitol to particle size smaller than 300 microns, and mixing with the mixed powder to form a third mixture;
Finishing banana powder essence to reach a particle size of less than 250 mu m, finishing colloidal silicon dioxide to reach a particle size of less than 250 mu m, and then carrying out equal incremental mixing with the third mixture to form a fourth mixture;
3. Sub-packaging
And (5) packaging the fourth mixture into bags by a packaging machine.
Example 2
The other contents were the same as in example 1 except for the following.
Crushing the polycarbophil raw material to a particle size smaller than 100 mu m, adding glucan, uniformly mixing, and finishing grinding when the particle size of the mixture is smaller than 80 mu m.
Example 3
The other contents were the same as in example 1 except for the following.
Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Microcrystalline cellulose | 250g |
| Dextran | 437.5g |
| Cherry flavor essence | 12.5g |
| Magnesium stearate | 37.5g |
Example 4
The other contents were the same as in example 1 except for the following.
Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Lactose and lactose | 237.5g |
| Dextran | 500g |
| Sweet orange flavor essence | 68.8g |
| Talc powder | 6.3g |
Example 5
Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Sorbitol | 94g |
| Dextran | 312g |
| Strawberry flavor essence | 75g |
| Colloidal silica | 18g |
Comparative example 1
The other contents were the same as in example 2 except for the following. Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Mannitol (mannitol) | 125g |
| Xanthan gum | 312.5g |
| Banana flavor essence | 50g |
| Colloidal silica | 12.5g |
Comparative example 2
The recipe is the same as in example 1.
The preparation process comprises the following steps:
grinding the prescription quantity of polycarbophil raw material by using a grinding ball with the diameter of 8mm, and taking out for standby when the particle size of the raw material is smaller than 100 mu m;
The mannitol and the glucan are processed in whole grain, the grain diameter is respectively smaller than 300 mu m and smaller than 250 mu m, and then the mannitol and the glucan are mixed with the crushed raw materials for standby after uniform mixing;
The banana essence and the colloidal silicon dioxide are respectively granulated, the grain diameters are respectively smaller than 250 mu m, and then the banana essence and the colloidal silicon dioxide are mixed with the mixed powder obtained in the previous step in an equal incremental way;
And finally, split charging by a split charging machine.
Comparative example 3
Prescription:
| raw and auxiliary materials | Dosage of |
| Polycarbophil calcium | 500g |
| Microcrystalline cellulose | 175g |
| Hydroxypropyl cellulose | 35g |
| Croscarmellose sodium | 75g |
| Colloidal silica | 5g |
| Magnesium stearate | 5g |
Preparing batches: 1 ten thousand tablets.
The preparation method comprises the following steps:
1. Uniformly mixing polycarbophil, microcrystalline cellulose, hypromellose and croscarmellose sodium, and granulating by a dry method;
2. Adding colloidal silicon dioxide and magnesium stearate into the granules obtained in the step1, uniformly mixing, and tabletting.
Comparative example 4
Prescription:
preparing batches: 1 ten thousand bags.
The preparation method comprises the following steps:
1. uniformly mixing polycarbophil, microcrystalline cellulose, hypromellose and croscarmellose sodium, and granulating with purified water by a wet method;
2. Adding colloidal silicon dioxide and magnesium stearate into the particles obtained in the step1, and uniformly mixing;
3. And (5) subpackaging: and (5) split charging by a split charging machine.
And (3) quality evaluation:
1. Sedimentation volume ratio test
According to the requirements of the fourth general rule oral suspension in Chinese pharmacopoeia 2020 edition, the sedimentation volume ratio is checked, and the specific method is as follows: taking a proper amount of a test sample, pouring the test sample into a 50ml measuring cylinder with a plug, adding water, shaking forcefully for 1min, recording the initial height H 0, and standing for 1, 3, 5, 7 and 12 hours to record the height H of which the H/H 0 is not lower than 0.9. The test results are shown in Table 1.
TABLE 1
As shown in Table 1, the dry suspension provided by the invention has good stability, and the sedimentation volume ratio within 12 hours after water is added meets the requirements of Chinese pharmacopoeia. In contrast, in comparative example 1, the stability of the suspension was significantly lowered after the dextran was changed to xanthan gum by the same process, but in comparative example 2, although dextran was used as the suspending agent, the suspending effect was also significantly impaired by the preparation process of the present invention.
2. Water absorption test
Taking 5 bags or 5 tablets, respectively taking tablet powder or dry suspension and a proper amount of granule content (about 200mg containing polycarbophil), placing into a weighed centrifuge tube with a plug, weighing the centrifuge tube and the original total weight of the content, then adding 35ml of 0.1mol/L hydrochloric acid solution, shaking for 30 minutes, centrifuging for 20 minutes, and discarding the supernatant. 35ml of 0.1mol/L hydrochloric acid solution was again added and shaken for 30 minutes, centrifuged for 20 minutes, and the supernatant was discarded. The above procedure was repeated by replacing the 0.1mol/L hydrochloric acid solution with water. Then 35ml of sodium bicarbonate solution with a mass concentration of 1.5% was added and shaken, the aeration was maintained to release the generated carbon dioxide, and the mixture was shaken for 1 hour, centrifuged and the supernatant was extracted by a syringe. 35ml of sodium bicarbonate solution with the mass percent of 1.5% is added again and shaken for 1 hour, standing overnight, centrifuging, discarding supernatant, weighing centrifuge tube and content, subtracting the original total weight, calculating to obtain the water absorption weight of the preparation (equivalent to the weight of 1g of polycarbophil raw material absorbing sodium bicarbonate solution), and recording the average value of water absorption force of 5 bags or 5 pieces of preparation, and the result is shown in table 2.
TABLE 2
| Example 1 | Example 2 | Comparative example 3 | Comparative example 4 | |
| Water absorbing capacity | 65g/g | 68g/g | 42g/g | 45g/g |
As shown in Table 2, the dry suspension of the invention has higher water absorption capacity, namely better water absorption expansion effect, than the polycarbophil tablet and the granule.
The test results show that the dry suspension provided by the invention solves the problems that a common solid preparation is not suitable for patients with dysphagia and has poor taste, improves the water absorption property of the preparation, exerts curative effect to the greatest extent, and is superior to other solid dosage forms.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (9)
1. The polycarbophil dry suspension is characterized by comprising the following raw materials in percentage by mass:
30% -60% of polycarbophil calcium
Dextran 20-50%
5 To 30 percent of diluent
1 To 10 percent of flavoring agent
0-3% Of glidant;
The particle size of the polycarbophil is smaller than 100 mu m, and the particle size of the glucan is smaller than 80 mu m;
The diluent is one or more of lactose, microcrystalline cellulose, mannitol and sorbitol;
The preparation method of the polycarbophil dry suspension comprises the following steps: crushing polycarbophil to a particle size of less than 100 mu m, adding glucan, mixing to form a first mixture, and crushing the first mixture to a particle size of less than 80 mu m to obtain a second mixture;
Finishing the diluent, and then mixing the diluent with the second mixture to form a third mixture;
respectively carrying out granule finishing treatment on the flavoring agent and the glidant, and then mixing with the third mixture to form a fourth mixture;
Subpackaging the fourth mixture.
2. The polycarbophil dry suspension according to claim 1, characterized in that the polycarbophil dry suspension comprises the following raw materials:
Polycarbophil calcium 50%
Dextran 31.3%
Diluent 12.5%
Taste corrigent 5%
1.2% Of glidant.
3. The polycarbophil dry suspension according to claim 1, wherein the particle size of the polycarbophil is 10-50 μm and the particle size of the dextran is 10-50 μm.
4. The polycarbophil dry suspension according to claim 1 or 2, characterized in that said flavouring is one or more of orange flavour, vanilla flavour, strawberry flavour, milk flavour, banana flavour, cherry flavour; and/or
The glidant is one or more of colloidal silicon dioxide, talcum powder and magnesium stearate.
5. A method of preparing the polycarbophil dry suspension of any one of claims 1-4, comprising the steps of:
Crushing polycarbophil to a particle size of less than 100 mu m, adding glucan, mixing to form a first mixture, and crushing the first mixture to a particle size of less than 80 mu m to obtain a second mixture;
Finishing the diluent, and then mixing the diluent with the second mixture to form a third mixture;
respectively carrying out granule finishing treatment on the flavoring agent and the glidant, and then mixing with the third mixture to form a fourth mixture;
Subpackaging the fourth mixture.
6. The method of claim 5, wherein the first mixture is formed by mixing the polycarbophil after being crushed to a particle size of less than 80 μm with dextran, and the second mixture is obtained by crushing the first mixture to a particle size of 10-50 μm.
7. The method of claim 5, wherein the sized flavoring agent and glidant are mixed with the third mixture in equal increments.
8. The method according to any one of claims 5 to 7, wherein the particle size of the particle size-conditioned diluent is not more than 300 μm, the particle size of the particle size-conditioned taste-masking agent is not more than 250 μm, and the particle size of the particle size-conditioned glidant is not more than 250 μm.
9. Use of the polycarbophil dry suspension of any one of claims 1-4 or prepared by the method of any one of claims 5-8 in the manufacture of a medicament for the treatment of irritable bowel syndrome.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5380522A (en) * | 1992-08-11 | 1995-01-10 | Day; Charles E. | Method for treatment of irritable bowel syndrome |
| US5618527A (en) * | 1992-09-30 | 1997-04-08 | Ascent Pediatrics Inc. | Calcium polycarbophil sprinkle |
| JP2004224758A (en) * | 2003-01-27 | 2004-08-12 | Abbott Japan Co Ltd | Calcium polycarbophil-containing preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110158930A1 (en) * | 2008-08-28 | 2011-06-30 | Astellas Pharma Inc. | Method for treatment of irritable bowel syndrome |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5380522A (en) * | 1992-08-11 | 1995-01-10 | Day; Charles E. | Method for treatment of irritable bowel syndrome |
| US5618527A (en) * | 1992-09-30 | 1997-04-08 | Ascent Pediatrics Inc. | Calcium polycarbophil sprinkle |
| JP2004224758A (en) * | 2003-01-27 | 2004-08-12 | Abbott Japan Co Ltd | Calcium polycarbophil-containing preparation |
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