CN112754999A - Bazedoxifene acetate composition and preparation method of bazedoxifene acetate film-coated tablet - Google Patents
Bazedoxifene acetate composition and preparation method of bazedoxifene acetate film-coated tablet Download PDFInfo
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- CN112754999A CN112754999A CN202110092160.3A CN202110092160A CN112754999A CN 112754999 A CN112754999 A CN 112754999A CN 202110092160 A CN202110092160 A CN 202110092160A CN 112754999 A CN112754999 A CN 112754999A
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- bazedoxifene acetate
- lactose
- microcrystalline cellulose
- antioxidant
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- OMZAMQFQZMUNTP-UHFFFAOYSA-N acetic acid;1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound CC(O)=O.C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 OMZAMQFQZMUNTP-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 229960003713 bazedoxifene acetate Drugs 0.000 title claims abstract description 57
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000007941 film coated tablet Substances 0.000 title claims abstract description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000000945 filler Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 14
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 14
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 14
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 14
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 14
- 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 13
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 13
- 239000008101 lactose Substances 0.000 claims abstract description 13
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 12
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 12
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 12
- 239000011718 vitamin C Substances 0.000 claims abstract description 12
- 239000000080 wetting agent Substances 0.000 claims abstract description 12
- 239000000853 adhesive Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000001070 adhesive effect Effects 0.000 claims abstract description 10
- 239000008213 purified water Substances 0.000 claims abstract description 9
- 239000000314 lubricant Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 239000002245 particle Substances 0.000 claims abstract description 5
- 239000003826 tablet Substances 0.000 claims description 19
- 238000005469 granulation Methods 0.000 claims description 11
- 230000003179 granulation Effects 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007884 disintegrant Substances 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 239000007888 film coating Substances 0.000 claims description 3
- 238000009501 film coating Methods 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 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 2
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 10
- 229930003427 Vitamin E Natural products 0.000 description 5
- 230000005496 eutectics Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 5
- 235000019165 vitamin E Nutrition 0.000 description 5
- 229940046009 vitamin E Drugs 0.000 description 5
- 239000011709 vitamin E Substances 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 239000008118 PEG 6000 Substances 0.000 description 3
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- 229960000817 bazedoxifene Drugs 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000008281 solid sol Substances 0.000 description 2
- 239000006104 solid solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 description 1
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 description 1
- 102100029951 Estrogen receptor beta Human genes 0.000 description 1
- 101001010910 Homo sapiens Estrogen receptor beta Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 240000004460 Tanacetum coccineum Species 0.000 description 1
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 235000008384 feverfew Nutrition 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Images
Classifications
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Abstract
The invention discloses a bazedoxifene acetate composition and a preparation method of a bazedoxifene acetate film-coated tablet, which relate to the technical field of medicines and comprise the following components in parts by weight: 20-26 parts of bazedoxifene acetate, 350 parts of filling agent, 30-50 parts of adhesive, 8-15 parts of disintegrating agent, 3-6 parts of antioxidant, 2-6 parts of glidant, 0.1-0.5 part of lubricant, 1-3 parts of wetting agent and a proper amount of purified water solvent, wherein the bazedoxifene acetate is a BCS II medicament, and the particle size D90 is 30 mu m; the antioxidant is vitamin C, the filler is composed of lactose and microcrystalline cellulose, and the proportion of the lactose to the microcrystalline cellulose is 1: 2-2: 1, the preparation method has the advantages of simple process, lower cost and easy industrial production.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to a bazedoxifene acetate composition and a preparation method of a bazedoxifene acetate film-coated tablet.
Background
The chemical name of bazedoxifene acetate is (1- [4- (2-azepan-1-yl-ethoxy) -benzyl ] -2- (4-hydroxy-phenyl) -3-methyl-1H-indole-5-ol acetic acid), having the chemical structure shown below:
it is a novel third-generation Selective Estrogen Receptor Modulators (SERMs) that competitively inhibits the binding of 17 β -estradiol to the estrogen receptors ER α and ER β, thereby activating the estrogen receptors of skeletal tissues and increasing the bone density of the spine and hip. The medicine is mainly used for preventing and treating osteoporosis of postmenopausal women, hardly stimulates breasts and uteruses, does not cause hyperplasia of mammary glands and endometrium, has definite curative effect, high tolerance and small toxic and side effect, is an ideal anti-osteoporosis medicine, and has wide market prospect.
Bazedoxifene was originally developed by hui, later assigned to the drug of feverfew, and has been marketed in italy and spain by the european drug administration at 27, 4 th 2009 under the trade name Conbriza, and in japan at 7 th 2010 under the trade name Viviant. The related preparation patent of the original research is not found.
Several compositions and formulation patents are also disclosed in the prior domestic technical patents to improve their stability in the composition and to promote or control the release of the drug. For example, Chinese patent publication No. CN201410109188.3 discloses a method for preparing sustained-release dripping pill preparation; chinese patent application No. CN201410109189.8 discloses a method for preparing a preparation by dispersing bazedoxifene acetate in a solid solution and/or a solid sol. Because bazedoxifene acetate is susceptible to oxidative degradation, antioxidants are added to the composition to improve the stability of the composition or the product of the formulation. Chinese patent publication No. CN201410109188.3 discloses a method for preparing sustained-release dripping pill preparation; chinese patent application No. CN201410109189.8 discloses a method for preparing a preparation by dispersing bazedoxifene acetate in a solid solution and/or a solid sol. In the examples of the available tablets in the prior patents, vitamin E TPGS is heated to melt, then bazedoxifene acetate is added and mixed uniformly, then PEG 6000 is added and mixed uniformly to form a suspension eutectic solution, the eutectic solution is cooled to room temperature and crushed to complete the mixing and granulation of the vitamin E and the bazedoxifene acetate, and the process is relatively complicated.
Disclosure of Invention
The invention aims to solve the problems in the existing preparation process of bazedoxifene acetate, and provides a bazedoxifene acetate composition and a preparation method of a bazedoxifene acetate film-coated tablet.
In order to achieve the above purpose, the invention adopts the technical scheme that:
a bazedoxifene acetate composition comprises, by weight, 20-26 parts of bazedoxifene acetate, 250-350 parts of a filler, 30-50 parts of an adhesive, 8-15 parts of a disintegrant, 3-6 parts of an antioxidant, 2-6 parts of a glidant, 0.1-0.5 part of a lubricant, 1-3 parts of a wetting agent and a proper amount of a purified water solvent, wherein the bazedoxifene acetate is a BCSII medicament, and the particle size D90 is 30 mu m; the antioxidant is vitamin C, the filler is composed of lactose and microcrystalline cellulose, and the proportion of the lactose to the microcrystalline cellulose is 1: 2-2: 1.
preferably, the composition comprises, by weight, 22.6 parts of bazedoxifene acetate, 310 parts of a filler, 44.6 parts of a binder, 12 parts of a disintegrant, 4.5 parts of an antioxidant, 4.5 parts of a glidant, 0.3 part of a lubricant, 1.5 parts of a wetting agent and the balance of a purified water solvent, wherein the bazedoxifene acetate is a BCS II medicament, and the particle size D90 is 30 microns; the antioxidant is vitamin C, the filler is composed of lactose and microcrystalline cellulose, and the proportion of the lactose to the microcrystalline cellulose is 1: 2-2: 1.
preferably, the ratio of lactose to microcrystalline cellulose is 1: 1.
preferably, the adhesive is pregelatinized starch, the disintegrant is one of sodium carboxymethyl starch and cross-linked sodium carboxymethyl starch, the glidant is silicon dioxide, the lubricant is magnesium stearate or talcum powder, and the wetting agent is sodium lauryl sulfate.
A method of preparing a film-coated tablet of bazedoxifene acetate comprising the steps of:
the method comprises the following steps: preparing a solution A, dissolving a wetting agent in a proper amount of purified water solvent according to the component proportion to prepare a solution A for later use;
step two: preparing a raw medicine mixture, and uniformly mixing bazedoxifene acetate and a filler disintegrant adhesive to prepare a raw medicine mixture B for granulation;
step three, granulating, namely adding the solution A into the original medicine mixture B prepared by uniformly mixing in the step two for granulating, drying at 50-60 ℃ and then finishing granules;
and step four, tabletting, namely adding additional auxiliary materials into the granules granulated in the step three, tabletting after total mixing, and coating to obtain the bazedoxifene acetate film-coated tablet preparation.
Preferably, the coating powder in the fourth step is non-functional light yellow gastric-soluble film coating.
The invention has the beneficial effects that:
1. compared with the prior art that vitamin E is adopted, but vitamin E (vitamin E) is a fat-soluble vitamin, in the embodiment of the tablet preparation in the prior patent, vitamin ETPGS is heated and melted, bazedoxifene acetate is added and uniformly mixed, PEG 6000 is added and uniformly mixed to form a suspension eutectic solution, the eutectic solution is cooled to room temperature and crushed to complete mixing and granulation of the vitamin E and the bazedoxifene acetate, and the process is relatively complicated.
2. In consideration of the instability of bazedoxifene acetate, the invention is a tablet which has more advantages and better stability compared with sustained-release dripping pills, granules and other dosage forms. And a fluidized bed granulation process is selected, and the application of the fluidized bed granulation technology is also suitable for enlarging production and improving yield. The present invention is a tablet that also has better stability during storage relative to other dosage forms. The invention adopts the fluidized bed granulation technology, the process is simple, the cost is lower, and the industrialized production is easy, furthermore, the invention adopts the coating powder as the non-functional gastric-soluble film coating, because the color of the tablet becomes yellow (the plain tablet is a white-like tablet) after the vitamin C in the prescription is oxidized, the beauty is influenced, the faint yellow coating powder is selected for coating, the drying temperature selected by the preparation process is 50-60 ℃, and the highest temperature in the preparation process is adopted. Compared with the prior patent, the preparation method has the advantages that after the vitamin ETPGS is heated and melted, the bazedoxifene acetate is added and mixed uniformly, then the PEG 6000 is added and mixed uniformly to form a suspension eutectic liquid, the temperature is kept at 80-85 ℃, the requirement on the preparation temperature condition is lower, the energy consumption is lower, and the stability of the bazedoxifene acetate tablet in the preparation process is improved.
Drawings
FIG. 1 is a dissolution profile of bazedoxifene acetate tablets;
Detailed Description
Example 1: prescription composition of bazedoxifene acetate tablets
Example 2: prescription composition of bazedoxifene acetate tablets
| Components | g/1000 tablets | In proportion% | Function(s) |
| Bazedoxifene acetate | 22.6 | 7.53 | |
| Lactose | |||
| 105 | 35 | Filler | |
| |
105 | 35 | Filler |
| Pregelatinized starch | 44.63 | 14.87 | Adhesive agent |
| Sodium carboxymethyl starch | 12 | 4 | Disintegrating agent |
| Vitamin C | 4.5 | 1.5 | Antioxidant agent |
| Sodium dodecyl sulfate | 4.5 | 1.5 | Wetting agent |
| Silicon dioxide | 0.3 | 0.1 | Glidants |
| Magnesium stearate | 1.5 | 0.5 | Lubricant agent |
Example 3: prescription composition of bazedoxifene acetate tablets
Description of the formulation process for bazedoxifene acetate tablets:
sodium dodecyl sulfate and purified water are prepared into a solution with the concentration of about 10 percent for standby.
The bazedoxifene acetate, the filling agent, the adhesive, the disintegrating agent and the antioxidant are weighed and mixed together, and after mixing, the wetting agent solution is added for wet granulation or fluidized bed granulation. Drying at 50-60 ℃ after granulation to control the water content to be 1-4%, and sieving with a 40-mesh sieve for granule finishing. Adding the rest materials, mixing, tabletting, and coating. Comparative example in vitro Release test of the prepared samples
Control sample: bazedoxifene acetate (specification 20mg) with the trade name Viviant, manufactured by Pfizer Japan Inc./ファイザー Kabushiki Kaisha, lot number CJ6968, package specification 10 pieces/plate; 10 plates/cassettes.
Experimental example samples: samples (specification 20mg) prepared according to example 2.
Experiment two: in vitro dissolution experiments were performed with the samples of example 2 and control samples to compare the in vitro release. The dissolution conditions were: pH6.8 phosphate buffer + 0.3% Tween 80, paddle 900ml, 50 rpm. The results are shown in FIG. 1.
The results show that the dissolution profile of example 2 is similar to the control sample, indicating that the compositions of the examples achieve in vitro release in a manner consistent with the control.
Experiment three: investigation of vitamin C in bazedoxifene acetate tablet composition
3.1. The prescription composition is as follows: the amount of vitamin C was adjusted on the basis of example 2, and the difference was adjusted by adding the amount of granulated microcrystalline cellulose to the formulation.
| Dosage of prescription | Prescription A (1500)Sheet) | Prescription B (1500 tablets) | Prescription C (1500 tablets) |
| Vitamin C (%) | 0.5 | 1.5 | 3.0 |
| Other raw and auxiliary materials | Same as example 1 | Same as example 1 | Same as example 1 |
3.2. Description of the preparation process:
sodium dodecyl sulfate and purified water are prepared into a solution with the concentration of about 10 percent for standby.
After being weighed, the bazedoxifene acetate, the filling agent, the adhesive, the disintegrating agent and the antioxidant are mixed together, and after being mixed, the wetting agent solution is added for fluidized bed granulation. Drying at 50-60 ℃ after granulation to control the water content to be 1-4%, and sieving by a 40-mesh sieve for granule finishing. Adding the rest materials, mixing, tabletting, and coating.
3.3. Stability test data:
the sample of formulation A, B, C was placed under the following conditions
Bazedoxifene acetate content change:
vitamin C change:
the results show that the content of the bazedoxifene acetate tablet (0-30 days) is not obviously reduced under the conditions of high temperature, high humidity and illumination by the composition formula (0.5-3%) added with the vitamin C, so that the stability is good, and the protective effect of the bazedoxifene acetate tablet can be exerted.
Claims (6)
1. A bazedoxifene acetate composition characterized by: the composition comprises, by weight, 20-26 parts of bazedoxifene acetate, 250-350 parts of a filling agent, 30-50 parts of an adhesive, 8-15 parts of a disintegrating agent, 3-6 parts of an antioxidant, 2-6 parts of a glidant, 0.1-0.5 part of a lubricant, 1-3 parts of a wetting agent and a proper amount of a purified water solvent, wherein the bazedoxifene acetate is a BCS II medicament, and the particle size D90 is 30 mu m; the antioxidant is vitamin C, the filler is composed of lactose and microcrystalline cellulose, and the proportion of the lactose to the microcrystalline cellulose is 1: 2-2: 1.
2. the bazedoxifene acetate composition of claim 1, wherein: each 1000 tablets of the preparation contains the following components in percentage by weight: 22.6 parts of bazedoxifene acetate, 310 parts of a filler, 44.6 parts of an adhesive, 12 parts of a disintegrant, 4.5 parts of an antioxidant, 4.5 parts of a glidant, 0.3 part of a lubricant, 1.5 parts of a wetting agent and the balance of a purified water solvent, wherein the bazedoxifene acetate is a BCS II medicament, and the particle size D90 is 30 microns; the antioxidant is vitamin C, the filler is composed of lactose and microcrystalline cellulose, and the proportion of the lactose to the microcrystalline cellulose is 1: 2-2: 1.
3. the bazedoxifene acetate composition of claim 1, wherein: the ratio of the lactose to the microcrystalline cellulose is 1: 1.
4. the bazedoxifene acetate composition of claim 1, wherein: the adhesive is pregelatinized starch, the disintegrating agent is one of sodium carboxymethyl starch and cross-linked sodium carboxymethyl starch, the glidant is silicon dioxide, the lubricant is magnesium stearate or talcum powder, and the wetting agent is sodium dodecyl sulfate.
5. A method of preparing a film-coated tablet of bazedoxifene acetate comprising the steps of:
the method comprises the following steps: preparing a solution A, dissolving a wetting agent in a proper amount of purified water solvent according to the component proportion to prepare a solution A for later use;
step two: preparing a raw medicine mixture, and uniformly mixing bazedoxifene acetate and a filler disintegrant adhesive to prepare a raw medicine mixture B for granulation;
step three, granulating, namely adding the solution A into the original medicine mixture B prepared by uniformly mixing in the step two for granulating, drying at 50-60 ℃ and then finishing granules;
and step four, tabletting, namely adding additional auxiliary materials into the granules granulated in the step three, tabletting after total mixing, and coating to obtain the bazedoxifene acetate film-coated tablet preparation.
6. A method of preparing a film-coated tablet of bazedoxifene acetate according to claim 5, wherein: the coating powder in the fourth step is non-functional light yellow gastric-soluble film coating.
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| CN113368075A (en) * | 2021-06-29 | 2021-09-10 | 郑州泰丰制药有限公司 | Bazedoxifene acetate tablets and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151026A (en) * | 2005-03-31 | 2008-03-26 | 惠氏公司 | O-desmethylvenlafaxine and bazedoxifene combination product and uses thereof |
| CN101304731A (en) * | 2005-08-24 | 2008-11-12 | 惠氏公司 | Bazedoxifene acetate formulations and preparation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151026A (en) * | 2005-03-31 | 2008-03-26 | 惠氏公司 | O-desmethylvenlafaxine and bazedoxifene combination product and uses thereof |
| CN101304731A (en) * | 2005-08-24 | 2008-11-12 | 惠氏公司 | Bazedoxifene acetate formulations and preparation method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368075A (en) * | 2021-06-29 | 2021-09-10 | 郑州泰丰制药有限公司 | Bazedoxifene acetate tablets and preparation method thereof |
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Application publication date: 20210507 |