CN117257747B - Bupropion hydrochloride tablet and preparation method thereof - Google Patents
Bupropion hydrochloride tablet and preparation method thereof Download PDFInfo
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- CN117257747B CN117257747B CN202311549965.1A CN202311549965A CN117257747B CN 117257747 B CN117257747 B CN 117257747B CN 202311549965 A CN202311549965 A CN 202311549965A CN 117257747 B CN117257747 B CN 117257747B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- IKBZAUYPBWFMDI-UHFFFAOYSA-N 5-bromo-4-methoxy-7-methyl-2,3-dihydro-1h-indene Chemical compound C1=C(Br)C(OC)=C2CCCC2=C1C IKBZAUYPBWFMDI-UHFFFAOYSA-N 0.000 title description 2
- 229960004367 bupropion hydrochloride Drugs 0.000 title description 2
- 229960001768 buspirone hydrochloride Drugs 0.000 claims abstract description 61
- 239000000463 material Substances 0.000 claims abstract description 61
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 claims abstract description 60
- 239000000314 lubricant Substances 0.000 claims abstract description 33
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 30
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 18
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 17
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 13
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 12
- 239000001116 FEMA 4028 Substances 0.000 claims abstract description 12
- 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 abstract description 12
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 12
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims abstract description 12
- 229960004853 betadex Drugs 0.000 claims abstract description 12
- 239000008101 lactose Substances 0.000 claims abstract description 12
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 10
- 229920003081 Povidone K 30 Polymers 0.000 claims abstract description 10
- 238000013329 compounding Methods 0.000 claims abstract description 10
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 10
- 239000000843 powder Substances 0.000 claims abstract description 10
- 229920000881 Modified starch Polymers 0.000 claims abstract description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 6
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims description 6
- 229940113116 polyethylene glycol 1000 Drugs 0.000 claims description 5
- -1 hydroxypropyl groups Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 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 claims description 3
- 229920003160 Eudragit® RS PO Polymers 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229920003163 Eudragit® NE 30 D Polymers 0.000 claims description 2
- 229920003156 Eudragit® RL PO Polymers 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims 1
- 229910021487 silica fume Inorganic materials 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 23
- 239000000377 silicon dioxide Substances 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 6
- 239000003826 tablet Substances 0.000 description 46
- 230000000052 comparative effect Effects 0.000 description 28
- 239000000203 mixture Substances 0.000 description 11
- 238000013268 sustained release Methods 0.000 description 11
- 239000012730 sustained-release form Substances 0.000 description 11
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 5
- 229920003134 Eudragit® polymer Polymers 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 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 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000007939 sustained release tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 229920003079 Povidone K 17 Polymers 0.000 description 1
- 229920003080 Povidone K 25 Polymers 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229940100487 povidone k25 Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention provides a buspirone hydrochloride tablet and a preparation method thereof, belonging to the technical field of medicine preparation, and comprising the following components in parts by weight: 20-30 parts of buspirone hydrochloride, 40-70 parts of slow release material, 5-10 parts of beta-cyclodextrin, 10-15 parts of lactose, 1-10 parts of lubricant and 10-25 parts of polyethylene glycol; wherein the slow release material comprises the following components in percentage by weight: (2-3): (0.3-0.8): (1.2-1.6) compounding hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol; the lubricant is one or more selected from silica powder microgel, magnesium stearate and pregelatinized starch. The buspirone hydrochloride tablet provided by the invention has the advantages of good slow release effect, low side effect, good tablet uniformity and long storage time, and can maintain good release degree within 24 hours.
Description
Technical Field
The invention belongs to the technical field of medicine preparation, and particularly relates to buspirone hydrochloride tablets and a preparation method thereof.
Background
Buspirone hydrochloride tablets are novel anxiolytic drugs which alter anxiety primarily by activating the serotonin (5-HT) 1A receptor in the brain. Is used for the auxiliary treatment of anxiety, depression, maladaptive behavior, and obsessive compulsive disorder. Buspirone hydrochloride tablets are mainly used for treating generalized anxiety disorder, have similar effects to benzodiazepine anxiolytic drugs in short time use, and do not damage cognitive functions after long-term administration, so that the buspirone hydrochloride tablets are relatively safe. The common side effects of buspirone hydrochloride tablets are nausea, vomiting and other gastrointestinal reactions, especially in the first week of administration. At present, the common buspirone hydrochloride tablet on the market has great side effect on the gastrointestinal tract, so that the sustained release tablet is more accepted and focused by people. However, the sustained release tablets sold in the market at present have the problem of poor release, and limit the use and development of the buspirone hydrochloride tablets.
Disclosure of Invention
Compared with the common tablet, the buspirone hydrochloride tablet has the advantages of good slow release effect, low side effect, good tablet uniformity and long storage time, and can maintain good release degree within 24 hours.
In order to achieve the above object, the present invention provides the following technical solutions:
buspirone hydrochloride tablets comprise the following components in parts by weight: 20-30 parts of buspirone hydrochloride, 40-70 parts of slow release material, 5-10 parts of beta-cyclodextrin, 10-15 parts of lactose, 1-10 parts of lubricant and 10-25 parts of polyethylene glycol; wherein the slow release material is selected from one or more of hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol; the lubricant is one or more selected from silica powder microgel, magnesium stearate and pregelatinized starch; the mass ratio of the bupirisone hydrochloride, the slow-release material, the lubricant and the polyethylene glycol is 5: (9-10): (1-1.5): (3-4).
Further, the slow release material is prepared from the following components in percentage by weight: (2-3): (0.3-0.8): (1.2-1.6), hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol.
The viscosity of the polyvinyl alcohol is 18.9 mPa.s. Purchased from Sichuan Baichun technology Co., ltd.
In the existing buspirone hydrochloride tablet, only a single type of slow-release material is generally used, and even if the same type of slow-release material is compounded with different types of materials, the slow-release effect is not ideal, the balanced slow-release effect within 24 hours is difficult to realize, and the gastric irritation is large. The invention is characterized by adding the following components in percentage by weight: (2-3): (0.3-0.8): the hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol compound sustained-release material (1.2-1.6) can play a synergistic effect by compounding a plurality of specific sustained-release materials, so that the buspirone hydrochloride tablet has a better sustained-release effect, can realize balanced sustained release within 24 hours, and can relieve the stimulation to intestines and stomach. The hypothesis is that three different types of slow release materials are compounded to play a role in synergy, so that a composite slow release system can be formed, and a more complex and accurate slow release effect is realized. However, the inventors found that buspirone hydrochloride tablets have poor sustained release effect after long-term storage.
The polyacrylic resin material comprises the following components in percentage by mass (2-4): (5-7): 1, the Uttky RS PO, uttky RL PO and Uttky NE 30D.
The Uttky RL PO is the brand name and brand name: EUDRAGIT ® Eud special ® RL PO DMF # 1242; the Uttky RS PO is the brand name and brand name: EUDRAGIT ® Eud special ® RS PO DMF # 1242; the Uttky NE 30D is the brand name and brand name: EUDRAGIT ® Eud special ® NE 30D DMF# 2822. The polyacrylic resin material selected by the invention uses medicinal resin EUDRAGIT ® Eud special ® It has a chemical composition of a specific mass ratio, wherein the chemical composition of the ewing RL PO is: ethyl acrylate, methyl methacrylate, trimethylaminoethyl methacrylate chloride copolymer ratio (1:2:0.2); the chemical composition ratio of the Eudragit RS PO is ethyl acrylate, methyl methacrylate and trimethylaminoethyl methacrylate chloride copolymer (1:2:0.1); the chemical composition of the ewing NE 30D is: ethyl acrylate, methyl methacrylate (2:1) copolymers. The above raw materials are mixed according to a specific proportion and then added into a slow-release material, so that the slow-release material has a very good slow-release effect, and the effect of the invention cannot be achieved by using other materials.
Further, the lubricant is a mixture of (1-3): (4-6): 1, compounding silica powder microgel, magnesium stearate and pregelatinized starch.
Further, the polyethylene glycol is selected from one or more of polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000 or polyethylene glycol 4000.
Further, the polyethylene glycol is in a mass ratio of (2-4): 1: (0.2-0.5) polyethylene glycol 400, polyethylene glycol 1000 and polyethylene glycol 4000.
Through a large number of experiments, the invention is found that the lubricant, the polyethylene glycol and the slow release material are compounded in specific types and proportions, and the mass ratio of the polyacrylic resin material is 1: (2-4): when the Eudragit RS PO, eudragit RL PO and Eudragit NE 30D of (5-7) are compounded, the storage performance of the buspirone hydrochloride tablet after long-term storage can be improved, and the tablet still has a good slow-release effect after 6 months of storage. However, the storage performance of the prepared buspirone hydrochloride tablet is not ideal after the types and the proportions of the lubricant and the polyethylene glycol are changed or after the composition of the polyacrylic resin material is changed. It is hypothesized that by compounding the specific raw materials to generate synergistic effect, the storage stability of the slow-release material can be increased, the internal structure of the buspirone hydrochloride tablet is more stable, and the storage life can be prolonged.
Further, the hydroxypropyl methylcellulose contains 19-24 wt% of methoxy and 4.0-12 wt% of hydroxypropyl. Purchased from the company of the western medicine auxiliary materials, inc: k15, substitution 2208. In order to improve the bioavailability of the buspirone hydrochloride tablet, the hydroxypropyl methylcellulose with methoxy and hydroxypropyl contents is specifically selected, so that the drug effect can be better realized.
Further, the grain diameter of the silica powder microgel is 100-150 meshes.
The silica powder microgel is purchased from Qingdan Xin Yonglai silica gel limited company.
Further, the mass ratio of the buprenone hydrochloride, the slow release material, the lubricant and the polyethylene glycol is 5:9:1:3.
the inventor finds that when the buspirone hydrochloride is mixed with a sustained-release material formed by specific components, a lubricant and polyethylene glycol in a specific proportion, the prepared buspirone hydrochloride tablet has better uniformity, and the components or the proportion of a certain raw material are changed to influence the uniformity, so that the raw materials are suspected to be matched together, the mixing performance of a raw material system can be improved, and the uniformity is improved.
Further, the composition comprises the following components in parts by weight: 25 parts of buspirone hydrochloride, 45 parts of slow release material, 9 parts of beta-cyclodextrin, 12 parts of lactose, 5 parts of lubricant and 15 parts of polyethylene glycol.
The invention also provides a preparation method of the buspirone hydrochloride tablet, which comprises the following steps: the bupirisone hydrochloride, the slow release material, beta-cyclodextrin, lactose, lubricant and polyethylene glycol are uniformly mixed and granulated in a granulator; and drying the granules in a drying device, and tabletting to obtain the buspirone hydrochloride tablets.
The raw materials of the invention are common pharmaceutical excipients and are commercially available.
Compared with the prior art, the invention has the advantages that:
1. compared with the common tablet, the buspirone hydrochloride tablet has the advantages of good slow release effect, low side effect, good tablet uniformity and long storage time, and maintains good release degree within 24 hours.
2. The invention is characterized by adding the following components in percentage by weight: (2-3): (0.3-0.8): the sustained release material compounded by the hydroxypropyl methylcellulose, the povidone K30, the polyacrylic resin material and the polyvinyl alcohol in the (1.2-1.6) ensures that the buspirone hydrochloride tablet has better sustained release effect and can relieve the stimulation to intestines and stomach.
3. According to the invention, by compounding the lubricant, the polyethylene glycol and the slow-release material in specific types and proportions, the storage performance of the buspirone hydrochloride tablet after long-term storage can be improved, and the slow-release effect is kept better.
4. When the buspirone hydrochloride is mixed with a slow release material formed by specific components, a lubricant and polyethylene glycol according to a specific proportion, the prepared buspirone hydrochloride tablet has better uniformity.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. 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.
Example 1
The embodiment provides a buspirone hydrochloride tablet, which comprises the following components in parts by weight: 25 parts of buspirone hydrochloride, 45 parts of slow release material, 9 parts of beta-cyclodextrin, 12 parts of lactose, 5 parts of lubricant and 15 parts of polyethylene glycol.
The slow release material comprises the following components in percentage by weight: 2.6:0.5:1.4, hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol.
The polyacrylic resin material is characterized by comprising the following components in percentage by mass: 5.9:1, the Uttky RS PO, uttky RL PO and Uttky NE 30D.
The weight ratio of the lubricant is 2:5:1, compounding silica powder microgel, magnesium stearate and pregelatinized starch.
The polyethylene glycol is prepared from the following components in percentage by mass: 1:0.4 of polyethylene glycol 400, polyethylene glycol 1000 and polyethylene glycol 4000.
19-24% of methoxy groups in the hydroxypropyl methyl cellulose and 4.0-12% of hydroxypropyl groups.
The grain diameter of the silica powder microgel is 100 meshes.
The embodiment also provides a preparation method of the buspirone hydrochloride tablet, which comprises the following steps: the bupirisone hydrochloride, the slow release material, beta-cyclodextrin, lactose, lubricant and polyethylene glycol are uniformly mixed and granulated in a granulator; and drying the granules in a drying device, and tabletting to obtain the buspirone hydrochloride tablets.
Example 2
The differences between this embodiment and embodiment 1 are: buspirone hydrochloride tablets comprise the following components in parts by weight: 20 parts of buspirone hydrochloride, 40 parts of slow release materials, 8 parts of beta-cyclodextrin, 12 parts of lactose, 4 parts of lubricants and 16 parts of polyethylene glycol.
Example 3
The differences between this embodiment and embodiment 1 are: the slow release material comprises the following components in percentage by weight: 2:0.3: 1.6, hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol.
Comparative example 1
The difference between this comparative example and example 1 is: buspirone hydrochloride tablets comprise the following components in parts by weight: 22 parts of buspirone hydrochloride, 36 parts of slow release materials, 12 parts of beta-cyclodextrin, 10 parts of lactose, 7 parts of lubricant and 38 parts of polyethylene glycol.
Comparative example 2
The difference between this comparative example and example 1 is: buspirone hydrochloride tablets comprise the following components in parts by weight: 23 parts of buspirone hydrochloride, 65 parts of slow release materials, 9 parts of beta-cyclodextrin, 12 parts of lactose, 9 parts of lubricants and 17 parts of polyethylene glycol.
Comparative example 3
The difference between this comparative example and example 1 is: the slow release material comprises the following components in percentage by weight: 1:1:1, hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol.
Comparative example 4
The difference between this comparative example and example 1 is: the slow release material comprises the following components in percentage by weight: 2:0.5:1.5, povidone K15, povidone K30, povidone K25 and povidone K17.
Comparative example 5
The difference between this comparative example and example 1 is: the weight ratio of the lubricant is 1:1:1, compounding silica powder microgel, magnesium stearate and pregelatinized starch.
Comparative example 6
The difference between this comparative example and example 1 is: the weight ratio of the lubricant is 2:4:1, talcum powder, magnesium stearate and pregelatinized starch.
Comparative example 7
The difference between this comparative example and example 1 is: the polyethylene glycol is prepared from the following components in percentage by mass: 1:1, polyethylene glycol 400, polyethylene glycol 1000 and polyethylene glycol 4000. The weight ratio of the lubricant is 1:1:1, compounding silica powder microgel, magnesium stearate and pregelatinized starch.
Comparative example 8
The difference between this comparative example and example 1 is: the polyethylene glycol is prepared from the following components in percentage by mass: 1:0.3 polyethylene glycol 400, polyethylene glycol 600 and polyethylene glycol 4000. The weight ratio of the lubricant is 2:4:1, talcum powder, magnesium stearate and pregelatinized starch.
Comparative example 9
The difference between this comparative example and example 1 is: the mass ratio of the polyacrylic resin material is 3:1, the Uttky RS PO and Uttky RL PO are compounded.
Performance testing
1. The dissolution rate (dissolution mass/(total amount of drug) ×100%) of buspirone hydrochloride tablets prepared in examples and comparative examples were measured by dissolution rate measurement (second appendix XC first method of chinese pharmacopoeia 2000 edition) respectively. The control group was a tablet of buspirone hydrochloride, produced by Jiangsu-enhua pharmaceutical industry Co., ltd, and each sample was sampled at 1h, 4h, 8h, 12h, 16h, 20h, 24h, and the results are shown in Table 1, in which/representative the time point was no longer examined.
TABLE 1 dissolution rate of buspirone hydrochloride tablets (%)
As shown in examples 1-3 and comparative examples 1-9, buspirone hydrochloride tablets of the present invention have a sustained release effect.
As can be seen from comparative examples 3 and 4, the composition and the ratio of the slow release material are changed to reduce the slow release effect.
2. The products of the examples and the comparative examples were stored in a sealed light-tight manner for 6 months, and the comparative group was a Yishu-buspirone hydrochloride tablet manufactured by Jiangsu Enhua pharmaceutical industry Co., ltd. The results are shown in Table 2.
Table 2 dissolution rate (%)
As shown in examples 1-3 and comparative examples 1-9, the buspirone hydrochloride tablet of the present invention has a good slow release effect after being stored for 6 months.
From comparative examples 5 to 9, it can be seen that the composition and the proportion of the sustained-release material are changed, and the sustained-release effect after 6 months of storage is damaged to different degrees by the change of the lubricant and the polyethylene glycol, which shows that the synergistic effect among the raw materials has an influence on the stability of the buspirone hydrochloride tablet, and the composition and the proportion of the polyacrylic resin material have a relatively obvious influence on the stability.
3. The buspirone hydrochloride tablets prepared in examples and comparative examples were subjected to content uniformity measurement (calculation formula=a+1.8s, wherein a is the absolute value of the difference between the labeling amount and the mean value, and S is the difference between the high performance liquid chromatography) using high performance liquid chromatography, according to the rule of the content uniformity inspection method of appendix XE of edition two of chinese pharmacopoeia 2010, and each group was subjected to measurement of 10 tablets. The control group was a tablet of buspirone hydrochloride, a product of Jiangsu Enhua pharmaceutical Co., ltd. The results are shown in Table 3.
TABLE 3 content uniformity test results
As shown in examples 1-3 and comparative examples 1-9, the buspirone hydrochloride tablet of the present invention has excellent uniformity, which is significantly lower than the specification of A+1.8S.ltoreq.15.
As is clear from comparative examples 1 to 9, the uniformity is reduced by changing the proportions of buspirone hydrochloride and the slow-release material, lubricant and polyethylene glycol, and the composition of the buspirone hydrochloride and the slow-release material, lubricant and polyethylene glycol.
While the foregoing is directed to the preferred embodiments of the present invention, it will be appreciated by those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the present invention.
Claims (5)
1. Buspirone hydrochloride tablets are characterized by comprising the following components in parts by weight: 20-30 parts of buspirone hydrochloride, 40-70 parts of slow release material, 5-10 parts of beta-cyclodextrin, 10-15 parts of lactose, 1-10 parts of lubricant and 10-25 parts of polyethylene glycol;
wherein the slow release material comprises the following components in percentage by weight: (2-3): (0.3-0.8): the hydroxypropyl methylcellulose, povidone K30, polyacrylic resin material and polyvinyl alcohol of (1.2-1.6) are compounded, wherein the polyacrylic resin material is prepared from the following components in percentage by mass (2-4): (5-7): 1, an Eudragit RS PO, an Eudragit RL PO and an Eudragit NE 30D are compounded;
the mass ratio of the bupirisone hydrochloride, the slow-release material, the lubricant and the polyethylene glycol is 5: (9-10): (1-1.5): (3-4);
the weight ratio of the lubricant is (1-3): (4-6): 1, compounding micro silica gel, magnesium stearate and pregelatinized starch;
the polyethylene glycol is prepared from the following components in percentage by mass (2-4): 1: compounding polyethylene glycol 400, polyethylene glycol 1000 and polyethylene glycol 4000 (0.2-0.5);
19-24 wt% of methoxy groups in the hydroxypropyl methyl cellulose and 4.0-12 wt% of hydroxypropyl groups.
2. Buspirone hydrochloride tablet according to claim 1, characterized in that the particle size of the micro powder silica gel is 100-150 mesh.
3. Buspirone hydrochloride tablet according to claim 1, characterized in that the mass ratio of buspirone hydrochloride, slow release material, lubricant and polyethylene glycol is 5:9:1:3.
4. buspirone hydrochloride tablet according to claim 1, characterized by comprising the following components in parts by weight: 25 parts of buspirone hydrochloride, 45 parts of slow release material, 9 parts of beta-cyclodextrin, 12 parts of lactose, 5 parts of lubricant and 15 parts of polyethylene glycol.
5. A process for the preparation of buspirone hydrochloride tablets according to any of claims 1 to 4, characterized by comprising the steps of: the bupirisone hydrochloride, the slow release material, beta-cyclodextrin, lactose, lubricant and polyethylene glycol are uniformly mixed and granulated in a granulator; and drying the granules in a drying device, and tabletting to obtain the buspirone hydrochloride tablets.
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| KR20100077959A (en) * | 2008-12-29 | 2010-07-08 | 윤국렬 | Controlled release pharmaceutical formulation for oral administration of anxiolytic drug |
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