CN1634079A - Compound estradiol valerate tablet and its preparation process - Google Patents
Compound estradiol valerate tablet and its preparation process Download PDFInfo
- Publication number
- CN1634079A CN1634079A CN 200410094874 CN200410094874A CN1634079A CN 1634079 A CN1634079 A CN 1634079A CN 200410094874 CN200410094874 CN 200410094874 CN 200410094874 A CN200410094874 A CN 200410094874A CN 1634079 A CN1634079 A CN 1634079A
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- China
- Prior art keywords
- tablet
- estradiol valerate
- compound
- compound estradiol
- disintegrating agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960004766 estradiol valerate Drugs 0.000 title claims abstract description 45
- -1 Compound estradiol valerate Chemical class 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 claims abstract description 22
- 229940053934 norethindrone Drugs 0.000 claims abstract description 14
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 12
- 239000011230 binding agent Substances 0.000 claims abstract description 9
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 29
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 20
- 229920002472 Starch Polymers 0.000 claims description 18
- 239000008107 starch Substances 0.000 claims description 18
- 235000019698 starch Nutrition 0.000 claims description 18
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 239000008187 granular material Substances 0.000 claims description 14
- 239000008101 lactose Substances 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 14
- 239000000741 silica gel Substances 0.000 claims description 14
- 229910002027 silica gel Inorganic materials 0.000 claims description 14
- 239000002671 adjuvant Substances 0.000 claims description 10
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 229960003943 hypromellose Drugs 0.000 claims description 6
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims 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 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229940005605 valeric acid Drugs 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 abstract description 3
- 239000000470 constituent Substances 0.000 abstract 1
- 229920003081 Povidone K 30 Polymers 0.000 description 10
- 238000004090 dissolution Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 230000001476 alcoholic effect Effects 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 238000003113 dilution method Methods 0.000 description 6
- 238000005507 spraying Methods 0.000 description 6
- 238000000227 grinding Methods 0.000 description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical class 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 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 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 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound estradiol valerate tablet and its preparation process, wherein the active constituents of the tablet include oestradiol valerate and norethisterone, and at least include a crumbling agent, a soluble deflocculating agent with binding property, a binding agent and a lubricating agent. The tablet has rather good bioavailability in vivo and increased dissolving degree externally.
Description
Technical field
The present invention relates to a kind of compound estradiol valerate tablet, the present invention also relates to produce the method for this tablet.
Background technology
Because of estradiol valerate is the valerate of estradiol, almost insoluble in water, the tablet of preparation method preparation routinely, its bioavailability is low, influences clinical efficacy.
Summary of the invention
Purpose of the present invention mainly provides the compound estradiol valerate tablet that has improved bioavailability, and this tablet constant product quality has better hardness simultaneously, both can be convenient to packing and transportation, is convenient to suitability for industrialized production again.This tablet has improved bioavailability in vivo, at the external dissolution that improved.
For achieving the above object, the present invention has adopted following technical scheme:
A kind of compound estradiol valerate tablet, the active component of compound estradiol valerate tablet are estradiol valerate and norethindrone, and comprise the solubility diluent of a kind of disintegrating agent, a kind of tool adhesion characteristic, a kind of binding agent and a kind of lubricant at least.
Wherein each components contents is 1%～40% valeric acid two pure and mild norethindrone mixture, 3%～30% disintegrating agent, 40%～90% solubility diluent, 0.1～5% binding agent and 0.5%～2% lubricant.
Described disintegrating agent is selected from low-substituted hydroxypropyl cellulose, starch, polyvidone, carboxymethyl starch sodium, crospovidone and their mixture.
Described solubility diluent is selected from lactose, mannitol, xylitol, Sorbitol and maltose alcohol.
Described binding agent is optional from polyvidone, hypromellose, sodium carboxymethyl cellulose, starch slurry, preferably from the polyvidone of the different degrees of cross linking.
Described lubricant is selected from magnesium stearate, sodium stearyl fumarate, stearic acid, Pulvis Talci, micropowder silica gel.
The invention also discloses a kind of preparation method of compound estradiol valerate tablet, at first, adopt with disintegrating agent again and granulate, mix with other adjuvant again active substance estradiol valerate and norethindrone raw material micronizing, adopt conventional sheeting equipment to carry out tabletting, obtain meeting the tablet of movement requirement.
This method may further comprise the steps: with estradiol valerate raw material micronizing, adjuvant sieves (1); (2) with solubility diluent, the binding agent mix homogeneously of tool adhesion characteristic, get mixed accessories; (3) with after the mixing of above-mentioned steps gained material, add disintegrating agent, and mixed at high speed; (4) add lubricant, mixing tabletting.
The compound estradiol valerate tablet that the present invention obtains has bioavailability preferably in vivo, at the external dissolution that improved, and possesses suitable hardness, helps packing and transportation.
The specific embodiment
The present invention is described further below by specific embodiment.
Embodiment 1
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 49.0g
Starch 21.0g
Hypromellose 2.1g
Magnesium stearate 0.56g
Micropowder silica gel 0.19g
Make 1000 in tablet
Concrete preparation:
(1) former, adjuvant are crossed 100 mesh sieves.
(2) lactose, starch are pressed the recipe quantity mix homogeneously, get mixed accessories.
(3) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, and mixing adds hypromellose at last.
(4) mixed 3 minutes in the high-speed mixer high speed, it is an amount of that spraying adds pure water, granulates under suitable operating condition.
(5) wet granular adds magnesium stearate, micropowder silica gel, mixing, tabletting through 16 mesh sieve granulate.
Testing result:
(1) tablet that according to said method prepares, hardness is at 1.5-3kg;
(2) tablet that according to said method prepares, its friability is less than 1%.
(3) tablet that according to said method prepares, its dissolution is less than 60%.
Method: two appendix XC of Chinese Pharmacopoeia version in 2000 three therapeutic methods of traditional Chinese medicine is measured, phosphate buffer (two appendix XVD of Chinese Pharmacopoeia version in 2000) with the pH7.3 that contains 0.5% sodium lauryl sulphate is a dissolution medium, rotating speed is that per minute 100 changes, in the time of 120 minutes, it is an amount of to get solution, filters through filter membrane, adopts high effective liquid chromatography for measuring, calculate every stripping quantity respectively with internal standard method, the limit of norethindrone and estradiol valerate is respectively 80% and 70% of labelled amount.
Zhi Bei tablet according to said method, the dissolution of estradiol valerate 120 minutes was 35-60%.
Embodiment 2
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 49.0g
Starch 21.0g
Hypromellose 2.1g
Magnesium stearate 0.56g
Micropowder silica gel 0.19g
Make 1000 in tablet
Concrete preparation:
(1) with the ultra-fine grinding of estradiol valerate raw material process, adjuvant is crossed 100 mesh sieves.
(2) lactose, starch are pressed the recipe quantity mix homogeneously, get mixed accessories.
(3) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, and mixing adds hypromellose at last.
(4) mixed 3 minutes in the high-speed mixer high speed, it is an amount of that spraying adds pure water, granulates under suitable operating condition.
(5) wet granular adds magnesium stearate, micropowder silica gel, mixing, tabletting through 16 mesh sieve granulate.
Testing result:
(1) tablet that according to said method prepares, hardness is at 1.5-3kg;
(2) tablet that according to said method prepares, its friability is less than 1%.
(3) tablet that according to said method prepares, its dissolution is greater than 60%.
Zhi Bei tablet according to said method, the dissolution of estradiol valerate 120 minutes was 60-80%.
Embodiment 3
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 49.0g
Starch 21.0g
30 POVIDONE K 30 BP/USP 30 2.1g
Magnesium stearate 0.56g
Micropowder silica gel 0.19g
Make 1000 in tablet
Concrete preparation:
(1) with the ultra-fine grinding of estradiol valerate raw material process, adjuvant is crossed 100 mesh sieves.
(2) lactose, starch are pressed the recipe quantity mix homogeneously, get mixed accessories.
(3) 30 POVIDONE K 30 BP/USP 30 is mixed with 10% alcoholic solution.
(4) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, and mixing mixed 3 minutes in the high-speed mixer high speed, and the alcoholic solution of spraying adding 30 POVIDONE K 30 BP/USP 30 is an amount of, granulates under suitable operating condition.
(5) wet granular adds magnesium stearate, micropowder silica gel, mixing, tabletting through 16 mesh sieve granulate.Testing result:
(1) tablet that according to said method prepares, hardness is at 1.5-2.5kg;
(2) tablet of preparation according to said method, its friability is negative value less than 1%, for PVP draw wet due to.
(3) tablet that according to said method prepares, its dissolution is greater than 65%.
Embodiment 4
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 49.0g
Starch 21.0g
30 POVIDONE K 30 BP/USP 25 2.1g
Magnesium stearate 0.56g
Micropowder silica gel 0.19g
Make 1000 in tablet
Concrete preparation:
(1) with the ultra-fine grinding of estradiol valerate raw material process, adjuvant is crossed 100 mesh sieves.
(2) lactose, starch are pressed the recipe quantity mix homogeneously, get mixed accessories.
(3) 30 POVIDONE K 30 BP/USP 25 is mixed with 10% alcoholic solution.
(4) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, and mixing mixed 3 minutes in the high-speed mixer high speed, and the alcoholic solution of spraying adding 30 POVIDONE K 30 BP/USP 30 is an amount of, granulates under suitable operating condition.
(5) wet granular adds magnesium stearate, micropowder silica gel, mixing, tabletting through 16 mesh sieve granulate.
Testing result:
(1) tablet that according to said method prepares, hardness is at 1.5-2.5kg;
(2) tablet of preparation according to said method, its friability is negative value less than 1%, for PVP draw wet due to.
(3) tablet that according to said method prepares, its dissolution is greater than 70%.
Embodiment 5
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 31.0g
Starch 30.0g
Low-substituted hydroxypropyl methylcellulose 40.0g
Carboxymethylstach sodium 40.0g
30 POVIDONE K 30 BP/USP 25 4.5g
Magnesium stearate 0.56g
Micropowder silica gel 0.20g
Make 1000 in tablet
Concrete preparation:
(1) with the ultra-fine grinding of estradiol valerate raw material process, adjuvant is crossed 100 mesh sieves.
(2) take by weighing lactose, the starch of recipe quantity; The low-substituted hydroxypropyl methylcellulose of half recipe quantity, carboxymethylstach sodium, mix homogeneously gets mixed accessories.
(3) dimension ketone K25 is mixed with 10% alcoholic solution.
(4) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, mixing, and mixed at high speed 3 minutes again in high-speed mixer, it is an amount of that spraying adds the alcoholic solution of 30 POVIDONE K 30 BP/USP 25, granulates under suitable operating condition.
(5) wet granular adds low-substituted hydroxypropyl methylcellulose, the carboxymethylstach sodium of magnesium stearate, micropowder silica gel and surplus, mixing, tabletting through 16 mesh sieve granulate.
Testing result:
(1) tablet that according to said method prepares, hardness is at 2.5-4.0kg;
(2) tablet that according to said method prepares, its friability is less than 1%.
(3) tablet that according to said method prepares, its dissolution is greater than 85%.
Embodiment 6
The compound estradiol valerate tablet prescription is formed
Estradiol valerate 2.0g
Norethindrone 0.7g
Lactose 31.0g
Starch 30.0g
Carboxymethylstach sodium 40.0g
30 POVIDONE K 30 BP/USP 25 4.5g
Magnesium stearate 0.56g
Micropowder silica gel 0.20g
Make 1000 in tablet
Concrete preparation:
(1) with the ultra-fine grinding of estradiol valerate raw material process, adjuvant is crossed 100 mesh sieves.
(2) take by weighing lactose, the starch of recipe quantity; The carboxymethylstach sodium of half recipe quantity, mix homogeneously gets mixed accessories.
(3) dimension ketone K25 is mixed with 10% alcoholic solution.
(4) with two kinds of accurate weighings of medicine, mix homogeneously increases progressively dilution method with equivalent and adds mixed accessories, mixing, and mixed at high speed 3 minutes again in high-speed mixer, it is an amount of that spraying adds the alcoholic solution of 30 POVIDONE K 30 BP/USP 25, granulates under suitable operating condition.
(5) wet granular adds the carboxymethylstach sodium of magnesium stearate, micropowder silica gel and surplus, mixing, tabletting through 16 mesh sieve granulate.
Testing result:
(1) tablet that according to said method prepares, hardness is at 2.5-4.0kg;
(2) tablet that according to said method prepares, its friability is less than 1%.
(3) tablet that according to said method prepares, its dissolution is greater than 75%.
Claims (8)
1, a kind of compound estradiol valerate tablet, the active component that it is characterized in that compound estradiol valerate tablet is estradiol valerate and norethindrone, and comprises the solubility diluent of a kind of disintegrating agent, a kind of tool adhesion characteristic, a kind of binding agent and a kind of lubricant at least.
2. a kind of compound estradiol valerate tablet according to claim 1, it is characterized in that comprising 1%～40% valeric acid two pure and mild norethindrone mixture, 3%～30% disintegrating agent, 40%～90% solubility diluent, 0.1～5% binding agent and 0.5%～2% lubricant.
3, compound estradiol valerate tablet according to claim 2 is characterized in that described disintegrating agent is selected from low-substituted hydroxypropyl cellulose, starch, polyvidone, carboxymethyl starch sodium, crospovidone and their mixture.
4, compound estradiol valerate tablet as claimed in claim 2 is characterized in that described solubility diluent is selected from lactose, mannitol, xylitol, Sorbitol and maltose alcohol.
5, compound estradiol valerate tablet as claimed in claim 2 is characterized in that described binding agent is optional from polyvidone, hypromellose, sodium carboxymethyl cellulose, starch slurry, preferably from the polyvidone of the different degrees of cross linking.
6, compound estradiol valerate tablet as claimed in claim 2 is characterized in that described lubricant is selected from magnesium stearate, sodium stearyl fumarate, stearic acid, Pulvis Talci, micropowder silica gel.
7, the preparation method of compound estradiol valerate tablet as claimed in claim 1 or 2, it is characterized in that active substance estradiol valerate and norethindrone raw material micronizing, adopt with disintegrating agent again and granulate, mix with other adjuvant again, adopt conventional sheeting equipment to carry out tabletting, obtain meeting the tablet of movement requirement.
8, the preparation method of compound estradiol valerate tablet as claimed in claim 7 is characterized in that this method may further comprise the steps: with estradiol valerate raw material micronizing, adjuvant sieves (1); (2) with solubility diluent, the binding agent mix homogeneously of tool adhesion characteristic, get mixed accessories; (3) with after the mixing of above-mentioned steps gained material, add disintegrating agent, and mixed at high speed; (4) add lubricant, mixing tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100948744A CN100462078C (en) | 2004-11-18 | 2004-11-18 | Compound estradiol valerate tablet and its preparation process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100948744A CN100462078C (en) | 2004-11-18 | 2004-11-18 | Compound estradiol valerate tablet and its preparation process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1634079A true CN1634079A (en) | 2005-07-06 |
| CN100462078C CN100462078C (en) | 2009-02-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100948744A Expired - Fee Related CN100462078C (en) | 2004-11-18 | 2004-11-18 | Compound estradiol valerate tablet and its preparation process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100462078C (en) |
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2004
- 2004-11-18 CN CNB2004100948744A patent/CN100462078C/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| CN100462078C (en) | 2009-02-18 |
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Effective date of registration: 20100707 Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Co-patentee after: Zhejiang Ruida Pharmaceutical Co., Ltd. Patentee after: Hainan Pulin Pharmaceutical Co., Ltd. Co-patentee after: Hangzhou Saili Medicine Inst. Co., Ltd. Address before: 5, No. 9, building 167, building 310004, Ring North Road, Hangzhou, Zhejiang Patentee before: Fan Minhua |
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Correction item: Patentee Correct: Zhejiang Ridae Pharmaceutical Co., Ltd. False: Zhejiang Ruida Pharmaceutical Co., Ltd. Number: 33 Page: The title page Volume: 26 |
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