CN103385876B - Pharmaceutical composition of a kind of Frova and preparation method thereof - Google Patents
Pharmaceutical composition of a kind of Frova and preparation method thereof Download PDFInfo
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- CN103385876B CN103385876B CN201210138943.1A CN201210138943A CN103385876B CN 103385876 B CN103385876 B CN 103385876B CN 201210138943 A CN201210138943 A CN 201210138943A CN 103385876 B CN103385876 B CN 103385876B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 229940103547 frova Drugs 0.000 title claims abstract description 40
- XPSQPHWEGNHMSK-SECBINFHSA-N frovatriptan Chemical compound N1C2=CC=C(C(N)=O)C=C2C2=C1CC[C@@H](NC)C2 XPSQPHWEGNHMSK-SECBINFHSA-N 0.000 title claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 16
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 66
- 239000001384 succinic acid Substances 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 26
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 20
- 239000002671 adjuvant Substances 0.000 claims abstract description 19
- 239000007787 solid Substances 0.000 claims abstract description 12
- 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 abstract description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 10
- 239000008101 lactose Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
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- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 8
- 229950005770 hyprolose Drugs 0.000 claims abstract description 8
- 229960003943 hypromellose Drugs 0.000 claims abstract description 8
- 229920002472 Starch Polymers 0.000 claims abstract description 7
- 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 abstract description 7
- 239000008107 starch Substances 0.000 claims abstract description 7
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- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 6
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 6
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims abstract description 6
- 239000008187 granular material Substances 0.000 claims description 14
- 239000000314 lubricant Substances 0.000 claims description 12
- 238000009702 powder compression Methods 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 239000007779 soft material Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
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- 239000000080 wetting agent Substances 0.000 claims description 3
- 238000000465 moulding Methods 0.000 abstract description 4
- 239000002775 capsule Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 16
- 239000003826 tablet Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 8
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- 101710138639 5-hydroxytryptamine receptor 1B Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
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- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
- 102100027499 5-hydroxytryptamine receptor 1B Human genes 0.000 description 1
- WKEMJKQOLOHJLZ-UHFFFAOYSA-N Almogran Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CS(=O)(=O)N1CCCC1 WKEMJKQOLOHJLZ-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
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- 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 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
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- 208000001407 Vascular Headaches Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960002133 almotriptan Drugs 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
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- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 230000003920 cognitive function Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
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- 230000000630 rising effect Effects 0.000 description 1
- 229960000425 rizatriptan Drugs 0.000 description 1
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
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- 229960001360 zolmitriptan Drugs 0.000 description 1
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition making succinic acid Frova keep stable, said composition comprises: a. active component succinic acid Frova; B. other conventional solid preparation adjuvant, wherein other solid preparation molding adjuvant is selected from lactose, starch, hypromellose, copolyvidone, high two or more of hyprolose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, magnesium stearate, Pulvis Talci etc. of replacing; The invention also discloses the method for this pharmaceutical composition of preparation.<!--1-->
Description
Technical field
The present invention relates to pharmaceutical composition of a kind of Frova and preparation method thereof.Particularly relate to a kind of solid preparation of succinic acid Frova, as tablet, capsule and granule etc., and preparation method thereof.
Background technology
Migraine is a kind of repeatedly there is the vascular headache that inclined side or bilatenal headache are feature, and be a kind of clinical common chronic forms vascular illness, prevalence women is 3.3% ~ 32.6%, and male is 0.7% ~ 16.1%.Migraine is very large on the impact of quality of life, and the headache of the patient more than 1/2 can affect work or study, and the patient Ke Yin of nearly 1/3 has a headache and lacks work or absent from school.Migrainous recurrent exerbation also can cause decrease of cognitive function, is mainly the decline of verbal ability.Migraine, except disease itself can cause damage, can also cause other to damage further, if migraine is an independent hazard factor of apoplexy.Migraine also can be suffered from various diseases altogether, as epilepsy, depression and affective disorders.Women's migraine without aura patient occurs occurring together depression and depression, and comparatively Migraine without aura person is high for the ratio of anxiety.
Triptan medicine is migrainous first-line treatment medicine clinically, Frova is second filial generation triptan medicine, belong to selectivity 5HT1B and 5HT1D receptor subtype agonist, high affinity is had with 5HT1B and 5HT1D receptor, being most powerhouse in triptan medicine to the affinity of 5HT1B, mainly treating migrainous effect by suppressing brain overdistension that is outer and entocranial artery to reach.This product is similar to other triptan curative effect of medication, which overcome that first generation 5-HT1B/1D receptor stimulating agent oral administration biaavailability is low, the half-life is short, shortcoming (this product headache relapse rate is minimum in triptan medicine) that relapse rate is high, than rizatriptan, Zolmitriptan with the effect of Almogran is more lasting, toleration is better.Tested by pharmacological toxicology and clinical trial confirm, these product treatment migrainous evident in efficacy, safety is high.Be in adult, effective medicine of severe migraine, better medication can be provided to select for clinical.
This product is developed by GlaxoSmithKline company, after transfer Vernalis company.In June, 2002, commodity were called FROVA (EndoPharmaceuticals company obtains the attorneyship of this product in the U.S.) in U.S.'s Initial Public Offering, and clinical have for being grown up or the acute treatment of migraine of absence of aura.Now in the listing of multiple European countries such as Germany and Britain, and price is more expensive.At present, domesticly there is no this product list marketing, also have no the report declared and research and develop.In China, migrainous sickness rate is also in rising trend, and this product, as second filial generation triptan medicine, has that effect is more lasting, relapse rate is lower, the better advantage of toleration, better medication can be provided to select for clinical, also be conducive to patient and can use more economical first-line drug.Therefore, develop this product and there is good clinical value and more wide market prospect.
Summary of the invention
By research, we find, succinic acid Frova crude drug all has the obvious compatibility to react with most adjuvant under high temperature (60 DEG C), high humidity (75%) compound condition, in the former adjuvant ground selected by product (trade name: FROVA), microcrystalline Cellulose and carboxymethyl starch sodium all also have the obvious compatibility to react with raw material, formerly grind after product place 10 days with this understanding, related substance obviously increases (total impurities increases to 2.96% by 0.26%, and single maximum contaminant increases to 1.01% by 0.11%).In order to obtain the more stable product of quality, we are by principal agent succinic acid Frova and some adjuvant, as lactose, starch, hypromellose, copolyvidone, high hyprolose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, magnesium stearate, the Pulvis Talci etc. of replacing carry out compatibility, make oral solid formulation, as tablet, capsule, granule etc., there is good stability.
The object of this invention is to provide a kind of Pharmaceutical composition making succinic acid Frova keep stable.Said composition comprises a. active component succinic acid Frova; B. other solid preparation molding adjuvant.Diluent in wherein said solid preparation adjuvant is selected from one in lactose, starch or its mixture, and consumption is 40% ~ 90%, and preferably 70% ~ 90%.; Binding agent is selected from hypromellose, copolyvidone, high one or more of hyprolose of replacing, and consumption is 1% ~ 30%, and preferably 2% ~ 10%.; Disintegrating agent is selected from low-substituted hydroxypropyl cellulose, the one of polyvinylpolypyrrolidone or its mixture, and consumption is 1% ~ 25%, and preferably 3% ~ 8%; Lubricant be selected from magnesium stearate, Pulvis Talci one or both, consumption is 0.5% ~ 4.0%, preferably 0.5% ~ 2%.
Another object of the present invention is to provide a kind of preparation method making succinic acid Frova keep stable Pharmaceutical composition.First by principal agent succinic acid Frova and other solid preparation molding excipient, as lactose, low-substituted hydroxypropyl cellulose etc. are mixed; (1) add wetting agent or binding agent carries out wet granulation, the granule of preparation sieves after drying, tabletting after mixed with magnesium stearate, or fill capsule, or prepares granule; Or (2) adopt dry granulation direct compression process or direct powder compression to prepare tablet.Described preparation method specifically comprises:
A. get active component succinic acid Frova, with other solid preparation molding adjuvant a certain amount of, as lactose, low-substituted hydroxypropyl cellulose etc., cross 40 order to 80 mesh sieve mix homogeneously.
B. be wetting agent with water or non-aqueous matchmaker, or use certain density binding agent, above-mentioned mixed material is carried out soft material processed, cross 18 order to 20 mesh sieve wet granulars, wet granular dryly must do granule through 40 DEG C to 60 DEG C.Wherein non-aqueous matchmaker is the one in ethanol, acetone, is preferably ethanol; Binding agent is hypromellose, one or more replacement in hyprolose, copolyvidone high, and concentration is 1% ~ 10%.
C. in dry granule, add a certain amount of lubricant, cross 14 order to 16 mesh sieves and mix, containing active component Frova according to the compacting of clinical application demand is the tablet of 1%-5%, or directly capsule prepared by fill capsule, or direct packaging becomes granule.Wherein lubricant is preferably one in magnesium stearate, Pulvis Talci or its mixture, and consumption is 0.5% ~ 4.0% of whole weight of material.
D. the supplementary material mixture also a can prepared, after mixed with a certain amount of lubricant, adopt dry granulation process or technique of direct powder compression, directly prepares tablet or capsule without wet-granulation process.Wherein lubricant is preferably a kind of in magnesium stearate, Pulvis Talci or wherein several, and consumption is 0.5% ~ 4.0% of whole weight of material.
Detailed description of the invention
Below by way of detailed description of the invention, the present invention is further described.Here want to be pointed out that, detailed description of the invention below is only used for the present invention is described, those skilled in the art are under the prerequisite understanding spirit of the present invention, can carry out corresponding conversion according to the prior art of the art and knowledge to the present invention, these technical schemes all fall within scope of the present invention.
Embodiment 1
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 2
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 3
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 4
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 5
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 6
Formula:
Preparation technology:
Supplementary material is taken according to formula proportion, raw material and lactose, starch, copolyvidone, low-substituted hydroxypropyl cellulose were merged 60 mesh sieves to mixing homogeneously, adopt the alcoholic solution of 80% height to be replaced hyprolose and be mixed with the solution of 5% as binding agent, above-mentioned mixed material is carried out soft material processed, cross 18 order to 20 mesh sieve wet granulars, wet granular dryly must do granule through 40 DEG C to 60 DEG C.Dry granule adds polyvinylpolypyrrolidone and magnesium stearate mix homogeneously, and tabletting preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 7
Formula:
Preparation technology:
Supplementary material is taken according to formula proportion, raw material was merged 60 mesh sieves to mixing homogeneously with lactose, copolyvidone, low-substituted hydroxypropyl cellulose (inside adding), the alcoholic solution of 80% is adopted hypromellose to be mixed with the solution of 5% as binding agent, above-mentioned mixed material is carried out soft material processed, cross 18 order to 20 mesh sieve wet granulars, wet granular dryly must do granule through 40 DEG C to 60 DEG C.Dry granule adds low-substituted hydroxypropyl cellulose (additional) and magnesium stearate mix homogeneously, and tabletting preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Embodiment 8
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.Direct powder compression preparation is in flakes heavily 140mg, and sheet footpath is the succinic acid Frova tablet (also can directly fill No. 3 capsules prepare succinic acid Frova capsule) of 7mm.
Comparative example 1
Formula:
Preparation technology:
Taking supplementary material according to formula proportion, raw material and adjuvant being merged 60 mesh sieves to mixing homogeneously.It is 2.5mg that direct powder compression prepares specification, and sheet is heavily 140mg, and sheet footpath is the succinic acid Frova tablet of 7mm.
Experimental example 1 determination of related substances method (high performance liquid chromatography)
Chromatographic condition: immobile phase is WelchmaterialsAQC18 post (250 × 4.6mm, 5 μm), mobile phase is that 50mmol/L ammonium acetate buffer is (containing 0.5% triethylamine, with glacial acetic acid adjust pH 3.5)-acetonitrile (93:7), determined wavelength is 244nm, flow velocity is 1ml/min, and sample size is 20 μ l.
Related substance (catabolite) algoscopy: get test specimen 20, accurately weighed, porphyrize, it is appropriate that precision takes fine powder, adds suitable quantity of water and succinic acid Frova was dissolved in ultrasonic 5 minutes, then thin up makes the solution containing 0.1mg in every 1ml, filter, get subsequent filtrate as need testing solution.Precision measures need testing solution 20 μ l, injection liquid chromatography, and record chromatogram, to 3 times of main constituent peak retention time, measures its amount of degradation products (%) by areas of peak normalization method.
Experimental example 2 not packaged high-temperature sample high humidity influence factor stability compares
High temperature 60 DEG C is placed in by naked for all formulation samples (formula 1 to formula 4) of embodiment and comparative example, under relative humidity RH75% condition, respectively at sampling in 0 day, 5 days, 10 days, observe the appearance color change of preparation, and adopt the method for test example 1 to measure the change of the amount of its catabolite (related substance).The results are shown in Table 1.
The stability result of each formulation samples of table 1
Conclusion: from upper table 1, sample under acceleration conditions (temperature 60 C, relative humidity 75%) is placed after 5 days, 10 days, it is consistent with commercially available product that embodiment 1 to embodiment 8 sample quality is obviously better than the supplementary product kind that comparative example 1(adopts), be mainly manifested in the change of formulation aesthetics color and the change of catabolite.Comparative example 1 formulation aesthetics obviously variable color (becoming lark from white), catabolite obviously increases (total impurities increases to 1.52% by 0.14%, and single maximum contaminant increases to 1.01% by 0.07%); And embodiment 1 to embodiment 8 formulation aesthetics discoloration more weak (become by white I am light yellow), it is less (from changing the most obvious embodiment 7 that catabolite increases degree, total impurities increases to 0.81% by 0.18%, and single maximum contaminant increases to 0.35% by 0.13%).Therefore, the present invention is by after new recipe design, and preparation stability significantly improves.
Experimental example 3 is through the long-term stable experiment of aluminium-plastic bubble plate packing sample
After embodiment 4 and comparative example 1 are simulated commercially available product aluminium-plastic bubble plate packing, place at ambient temperature, carry out sample analysis every half a year, observe the appearance color change of preparation, and adopt the method for test example 1 to investigate the change of the amount of its catabolite (related substance).The results are shown in Table 2,3.
The stability result (formulation aesthetics color) of table 2 sample after aluminium-plastic bubble plate packing
The stability result (related substance) of table 3 sample after aluminium-plastic bubble plate packing
Conclusion: from table 2, table 3, embodiment 4 sample and comparative example 1 sample (supplementary product kind adopted is consistent with commercially available product) are after packaging, place 42 months at ambient temperature, formulation aesthetics color is all unchanged, but the change of catabolite differs greatly.After sample places 42 months at ambient temperature, comparative example 1 total impurities more than 1%, single maximum contaminant more than 2%, apparently higher than embodiment 4.Catabolite is non-active ingredient, but also may there is certain toxicity.Therefore, the present invention, by changing Yuan Yan factory formula, can obtain the product that quality is more stable, to reduce the risk of the untoward reaction caused because of catabolite, reaches the object extending limit date of using a drug after its production limit simultaneously.
Claims (9)
1. a succinic acid Frova pharmaceutical composition is 1% ~ 5% containing a. active component succinic acid Frova consumption; B. other conventional solid preparation adjuvant, the diluent in wherein said solid preparation adjuvant is selected from one in lactose, starch or its mixture, and consumption is 40% ~ 90%; Binding agent is selected from hypromellose, copolyvidone, one or more replacement in hyprolose high, and consumption is 1% ~ 30%; Disintegrating agent is selected from one in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone or its mixture, and consumption is 1% ~ 25%; Lubricant is selected from magnesium stearate, Pulvis Talci, in right amount.
2. pharmaceutical composition according to claim 1, is characterized in that the consumption of active component succinic acid Frova is 2% ~ 3%.
3. pharmaceutical composition according to claim 1, it is characterized in that diluent is selected from one in lactose, starch or its mixture, consumption is 70% ~ 90%.
4. pharmaceutical composition according to claim 1, it is characterized in that binding agent is selected from hypromellose, copolyvidone, one or more replacement in hyprolose high, consumption is 2% ~ 10%.
5. pharmaceutical composition according to claim 1, it is characterized in that disintegrating agent is selected from one in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone or its mixture, consumption is 3% ~ 8%.
6. the preparation method of pharmaceutical composition according to claim 1, comprising:
A. get active component succinic acid Frova and the solid preparation adjuvant except lubricant, cross 40 order to 80 mesh sieve mix homogeneously;
B. be wetting agent with water or non-aqueous matchmaker, above-mentioned mixed material is carried out soft material processed, cross 18 order to 20 mesh sieve wet granulars, wet granular dryly must do granule through 40 DEG C to 60 DEG C; Wherein non-aqueous matchmaker is selected from ethanol, acetone; Binding agent is selected from hypromellose, one or more replacement in hyprolose, copolyvidone high, and concentration is 1% ~ 10%;
C. in dry granule, add lubricant, cross 14 order to 16 mesh sieves and mix, granulate, makes preparation.
7. the preparation method of pharmaceutical composition according to claim 1, comprising:
A. get active component succinic acid Frova and the solid preparation adjuvant except lubricant, cross 40 order to 80 mesh sieve mix homogeneously;
B., by supplementary material mixture, after mixed with lubricant, dry granulation process or technique of direct powder compression is adopted to make preparation.
8., according to the preparation method of the pharmaceutical composition of claim 6 or 7, it is characterized in that lubricant is one or both in magnesium stearate, Pulvis Talci.
9. the preparation method of pharmaceutical composition according to claim 8, is characterized in that the consumption of lubricant is 0.5% ~ 2%.
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103976964B (en) * | 2014-05-16 | 2015-01-14 | 广东台城制药股份有限公司 | Erythromycin estolate tablet and preparation method thereof |
| CN104758268A (en) * | 2015-04-22 | 2015-07-08 | 青岛正大海尔制药有限公司 | Frovatriptan succinate tablet and preparation method thereof |
| CN109464408A (en) * | 2018-12-28 | 2019-03-15 | 正大制药（青岛）有限公司 | A kind of succinic acid SB 209509 piece |
| CN109528670B (en) * | 2018-12-28 | 2021-05-07 | 正大制药（青岛）有限公司 | Frovatriptan succinate tablet and preparation method thereof |
| CN110974801A (en) * | 2019-12-11 | 2020-04-10 | 正大制药（青岛）有限公司 | Frovatriptan succinate enteric-coated capsule and preparation method thereof |
| CN115998890A (en) * | 2023-02-01 | 2023-04-25 | 晨光生物科技集团股份有限公司 | Auxiliary material of traditional Chinese medicine extract tablet, traditional Chinese medicine extract tablet and preparation method thereof |
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Effective date of registration: 20160720 Address after: 650106 Kunming science and Technology Development Zone, Yunnan Province Road No. 45 Patentee after: Dihon Pharmaceutical Group Co., Ltd. Address before: 611731, No. 1, South Road, hi tech West, Sichuan, Chengdu Patentee before: Sichuan Dihon Medical Development Co., Ltd. Patentee before: Dihon Pharmaceutical Group Co., Ltd. |
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