CN109172534B - Nifedipine sustained-release tablet composition - Google Patents
Nifedipine sustained-release tablet composition Download PDFInfo
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- CN109172534B CN109172534B CN201811238357.8A CN201811238357A CN109172534B CN 109172534 B CN109172534 B CN 109172534B CN 201811238357 A CN201811238357 A CN 201811238357A CN 109172534 B CN109172534 B CN 109172534B
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
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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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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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
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
The invention relates to a nifedipine sustained-release tablet composition and a preparation method thereof. The nifedipine sustained-release tablet composition contains nifedipine, tween-80, lactose, microcrystalline cellulose and corn starch, wherein D90 of the nifedipine is 95-135 mu m, the mass ratio of the lactose to the nifedipine is within the range of 1.8:1-2.2:1, and the tween accounts for 6-9% of the total mass of a tablet core. According to the technical scheme, through reasonable component adjustment, the process and equipment limitations caused by over-fine crushing are avoided, and the tablet composition with the Cmax lower than that of a reference preparation and the AUC higher than that of the reference preparation is prepared.
Description
Technical Field
The invention relates to a nifedipine sustained-release tablet composition and a preparation method thereof, belonging to the technical field of pharmaceutical preparations.
Background
Hypertension is a common disease in China, needs to be taken for life, and has great influence on life health and living cost of people. Nifedipine is a old medicine for treating hypertension in the flat category, has huge market and good antihypertensive effect in China, and the sustained-release preparation can stably control the blood pressure of a human body, reduce the blood pressure fluctuation of a patient and has wide market prospect.
The nifedipine sustained-release tablet mostly adopts a sustained-release framework material to realize the sustained-release effect of nifedipine, but the original Bayer company patent (US 526446) discloses that the sustained-release effect can be achieved by utilizing the insoluble characteristic of nifedipine and controlling the specific surface area of nifedipine to be 1.0-4.0 m2(ii) in terms of/g. Calculated, the specific surface area of the nifedipine is 1.0m2D90 is less than 50 μm at/g. In the consistency evaluation work, in order to achieve the same bioavailability as the reference original preparation, a plurality of manufacturers can achieve the effectIn an imitation of the original patent, nifedipine is crushed by using a mechanical crushing device, and is subjected to airflow crushing to obtain the granularity D9050 microns below. In the actual work of the preparation, the nifedipine sustained-release tablet needs to strictly control the granularity of nifedipine, and the instability of the granularity can cause the instability of dissolution.
Disclosure of Invention
The invention aims to provide a nifedipine sustained-release preparation which is suitable for industrial production and has a sustained-release effect superior to that of the original research.
According to the general characteristics of insoluble drugs, the smaller the particle size, the faster the dissolution rate, and the technical scheme of the invention is discovered unexpectedly in the necessary prescription and process screening process for breaking through the original patents.
According to the technical scheme, the nifedipine tablet with high bioavailability is obtained through reasonable compatibility of nifedipine, tween-80, lactose, microcrystalline cellulose and corn starch. The D90 of the nifedipine is 95-135 mu m, the mass ratio of the lactose to the nifedipine bulk drug is within the range of 1.8:1-2.2:1, and the dosage of the Tween accounts for 6-9% of the total mass of the tablet core.
The technical scheme of the invention is as follows: a nifedipine sustained-release tablet composition contains nifedipine, Tween-80, lactose, microcrystalline cellulose and corn starch, wherein D90 of the nifedipine is 95-135 mu m, the mass ratio of the lactose to the nifedipine is within the range of 1.8:1-2.2:1, and the Tween accounts for 6-9% of the total mass of a tablet core.
Preferably, each thousand tablet compositions of the nifedipine sustained-release tablet composition comprise 20g of nifedipine with D90 of 95-135 μm, 36-44g of tween-805, 5g of corn starch, 8-12g of microcrystalline cellulose and 1g of magnesium stearate.
Preferably, each thousand tablet compositions of the nifedipine sustained-release tablet composition comprise 20g of nifedipine with D90 of 95-135 μm, 806 g of tween-806, 40g of lactose, 5g of corn starch, 8g of microcrystalline cellulose and 1g of magnesium stearate.
The preparation method of the composition disclosed by the invention is characterized in that the production process is protected from light, and the preparation method specifically comprises the following steps:
in the first step, nifedipine bulk drug is processed to the required particle size range.
And a second step of preparing an adhesive: preparing the corn starch with the prescription amount into a solution with the concentration of 2% -8%, preparing by adopting a pulp washing method, adding the Tween-80 with the prescription amount for standby, and uniformly stirring to be used as a bonding agent.
And thirdly, adding nifedipine and lactose in the prescription amount into a multifunctional fluidized bed, and granulating by using the slurry prepared in the second step.
And fourthly, after finishing the granules, uniformly mixing the granules with the microcrystalline cellulose with the prescription amount, adding magnesium stearate, uniformly mixing, and tabletting by using a phi 6 circular punch die.
Fifthly, film coating: weighing film coating powder (Carlekang, model 295F620084, hydroxypropyl methylcellulose, polyethylene glycol 4000, titanium dioxide, and ferric oxide), slowly adding into purified water, and fully dispersing. Coating the nifedipine tablets, wherein the weight of the coating is increased by 3-5%, so as to obtain the nifedipine sustained-release tablets.
According to the preparation method, the mixture of lactose and nifedipine with high water solubility is used as a carrier, so that the adhesive is uniformly dispersed on the carrier, and microcrystalline cellulose with capillary action is added subsequently, so that the phenomenon that high-dosage tween-80 forms a high-viscosity water barrier to hinder drug release is avoided. The microcrystalline cellulose is added in the form of dry powder, so that not only is the compressibility of the whole granule adjusted, but also the water absorption rate of the granule is adjusted, and the nifedipine is controlled to be released in a relatively low concentration in a human body.
The granularity of the nifedipine raw material medicine can be processed to the required granularity by adopting airflow crushing or other crushing modes and also by adopting a chemical crystallization method. Chemical crystallization methods are preferred.
The compositions of the present invention may also contain a proportion of lubricants, aesthetic/moisture resistant coatings and the like as necessary for glidant, anti-caking agents, fillers, suspending agents and the like in the preparation of good tablets of the general technical knowledge.
The composition is prepared into compressible granules by adopting a mode of orderly mixing part of raw auxiliary materials after fluidized bed granulation with the rest quantitative auxiliary materials, and a finished product is obtained after conventional tabletting and coating.
In general, nifedipine is used as an insoluble raw material medicine, the nifedipine is solubilized by micronization and surfactant addition, and a new section is formed on the nifedipine raw material medicine in the mechanical crushing process, so that the stability is adversely affected. In solving this problem, it has been unexpectedly found that the use of a small specific surface area, i.e. less than 1.0m of the original patent2/g（1.0m2The particle size D90 corresponding to the specific surface area is about 50 mu m), the corresponding particle size is nifedipine with large particle size, Tween-80 exceeding the conventional dosage, water-soluble auxiliary materials (such as lactose) with fixed proportion, microcrystalline cellulose with the functions of regulating water absorption rate and capillary and other auxiliary materials, and the composition is processed into tablets by the preparation process disclosed by the patent.
Has the advantages that:
according to the technical scheme, through reasonable component adjustment, the process and equipment limitations caused by over-fine crushing are avoided, the tablet composition with the Cmax lower than that of a reference preparation and the AUC higher than that of the reference preparation is prepared, and a high-quality medicine is provided for clinic.
The U.S. FDA approved drug inactive ingredient database regulations: the dosage of coated tablet Tween-80 is not more than 2.2 mg/dosage unit; the dosage of Tween-80 for oral administration is below 5%. Tests show that when the dosage of the preparation exceeds 5 percent, the dissolution rate of the oral preparation is reduced. The technical scheme of the invention adopts a large dosage of tween-80, thereby well improving the bioavailability of the nifedipine tablet and overcoming the defect that the dissolution is reduced on the contrary when the dosage of tween-80 exceeds 5 percent.
Clinical tests prove that the preparation prepared by the method has higher bioavailability compared with a reference preparation, and the wave crest and the wave trough of the blood concentration are relatively more stable, so that the nifedipine sustained-release tablet disclosed by the invention is stably released, the side effects of headache, facial flushing, edema and the like caused by too fast blood pressure reduction of nifedipine are reduced, the safety of medication is ensured, and the effective duration of the medicine is also ensured.
The product has the characteristics of lower cost (smaller specification), smaller side effect and the like for people taking the medicine for a long time or for a lifetime, and has the advantages of more robustness and better feasibility for commercial production.
Examples and comparative examples
Example 1
20g of nifedipine (105.5 mu m of D90), 40g of lactose, 5g of corn starch, 805 g of tween-805, 8g of microcrystalline cellulose, 1g of magnesium stearate and 4g of film coating premix (Carlekang, model 295F620084, and the components of hydroxypropyl methylcellulose, polyethylene glycol 4000, titanium dioxide and ferric oxide). 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Example 2 nifedipine 20g (105.5 μm for D90), lactose 44g, corn starch 5g, tween-807 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coated premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Example 3 nifedipine 20g (105.5 μm for D90), lactose 36g, corn starch 5g, tween-806 g, microcrystalline cellulose 12g, magnesium stearate 1g, film coated premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Example 4 nifedipine 20g (95.0 μm for D90), lactose 40g, corn starch 5g, tween-806 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coated premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Example 5 nifedipine 20g (135.2 μm for D90), lactose 40g, corn starch 5g, tween-806 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coated premix (carrekang, model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Comparative example 1 nifedipine 20g (105.5 μm for D90), lactose 50g, corn starch 5g, tween-807 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coating premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Comparative example 2 nifedipine 20g (105.5 μm for D90), lactose 30g, corn starch 5g, tween-806 g, microcrystalline cellulose 18g, magnesium stearate 1g, film coating premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Comparative example 3 nifedipine 20g (85.6 μm for D90), lactose 40g, corn starch 5g, tween-806 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coating premix (carrekang, model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Comparative example 4 nifedipine 20g (156.3 μm for D90), lactose 40g, corn starch 5g, Tween-806 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coating premix (Carlekang, model 295F620084, hydroxypropyl methylcellulose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Comparative example 5 nifedipine 20g (105.5 μm for D90), lactose 40g, corn starch 5g, tween-806 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coating premix (carrekang model 295F620084, ingredients hypromellose, polyethylene glycol 4000, titanium dioxide, iron oxide) 4 g. Mixing nifedipine, lactose and microcrystalline cellulose in a wet mixing granulator, adding an appropriate amount of adhesive (preparing starch slurry by a slurry washing method, adding tween-80, and dispersing uniformly) for granulation, drying by a fluidized bed, granulating, mixing, tabletting, and coating to prepare 1000 tablets.
Comparative example 6 nifedipine 20g (135.2 μm for D90), lactose 40g, corn starch 5g, Tween-804.2 g, microcrystalline cellulose 8g, magnesium stearate 1g, film coating premix (Carlekang, model 295F620084, hypromellose, polyethylene glycol 4000, titanium dioxide, iron sesquioxide) 4 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section of the specification.
Test example 1
The dissolution rates of the products of examples 1 to 5 and comparative examples 1 to 6 were measured for 15 minutes (min), 1 hour (h), 3 hours (h) and 12 hours (h), respectively, and a similarity factor f2 was calculated, and the data are shown in tables 1 and 2.
Release dissolution conditions: dissolution medium: 900ml of 0.3 percent Tween-80 aqueous solution (added by mass ratio and dissolved in water bath at 60 ℃), and the detection is carried out by high performance liquid chromatography with 75 turns of slurry method (2015 version XC second method which is an appendix of the second part of Chinese pharmacopoeia).
Dissolution profiles for examples 1-5 and the reference formulation are reported in table 1; the dissolution of comparative examples 1 to 6 is shown in Table 2.
Table 1 dissolution results of examples 1-5 and the reference formulation (n = 12)
TABLE 2 dissolution results of comparative examples 1 to 6 (n = 12)
Note that 1.f2 is a similarity factor and the value is higher than 50 (50-100), then the two curves can be identified as performance equivalents.
The reference formulation is selected from the same size oral tablets of the original research, according to the convention of the pharmaceutical development industry.
From the release results: examples 1-5 tween-80 in a super-conventional amount was uniformly dispersed in a starch slurry and sprayed on the surface of nifedipine to make the fine nifedipine and tween-80 physically closer to each other, thereby promoting the release of the drug.
The ratio of lactose to nifedipine is in the range of 1.8:1-2.2:1, the drug release effect is better, and outside the range, the release is too fast or slow. The particle size has obvious influence on the release of the medicine, and the patent process has obvious effect on the release promotion of the medicine with the same particle size of the raw material medicine. The mixture of lactose and nifedipine with high water solubility is used as a carrier to uniformly disperse the adhesive on the carrier, and microcrystalline cellulose with capillary action is added subsequently, so that high-dosage tween-80 is prevented from forming a high-viscosity water barrier to hinder the release of the medicament. And the microcrystalline cellulose is added in the form of dry powder, so that not only is the compressibility of the whole particles adjusted, but also the water absorption rate of the particles is adjusted, and the nifedipine is controlled to be released in a relatively low concentration in a human body.
Test example 2 fasting test before meal and postprandial test
Three preparations, three periods and a cross design are adopted. The elution periods (time >7 elimination half-lives) were all at least 3 days in this trial.
54 healthy adult subjects (1, the subjects are unlimited in sex, healthy and free of related system diseases, age is larger than or equal to 18 years old; 2, male weight is larger than or equal to 50kg, female weight is larger than or equal to 45kg, and body weight index is between 19-26 kg/m) meeting the selection standard are screened and randomly divided into 3 groups, 18 persons, 1 group and 2 groups in each group respectively take the products of example 4 and example 5, and 3 groups take reference preparations.
Fasting test before meal: subjects fasted overnight (over 10 hours) on an empty stomach before meals and took the product of example 4, the product of example 5 and the reference formulation on an empty stomach the next morning, respectively.
Postprandial experiments: the example 4, example 5 and reference formulations were each orally administered 30 minutes after a subject's meal with a high fat and high fever. The reference formulation was marketed by the japanese bayer company, beixintong, batch No. JPR 7269.
The test data are reported in table 3.
TABLE 3 fasting and postprandial test before meal (example 4, example 5 and reference formulations)
Table 3 the data illustrates: the results of fasting and postprandial experiments before meal show that the bioavailability (AUC (0-t), AUC (0- ∞)) and Cmax in vivo are related to the particle size of nifedipine used in the composition under the technology of the patent, within the particle size range set by the patent, the fasting and postprandial bioavailability are both higher, the Cmax is relatively low, the drug can realize sustained and stable drug release within the set particle size range, and the sustained release effect is lasting. And the slow release effect of the nifedipine prepared by the patent is more obvious.
Test example 3.
The sample of example 5 was administered to healthy adult males 6 times 1 tablet 1 time, 2 times daily for 15 consecutive days. Maximum, minimum and AUC after four administrations (after dinner on day 2)0-12hIn addition, on days 4, 8 and 15, the blood concentration is always above 10 ng/m L after administration for 12 hours, and effective blood concentration can be maintained by twice daily administration, which indicates that the medicine is safe and effective.
Claims (4)
1. The nifedipine sustained-release tablet composition is characterized by comprising nifedipine, tween-80, lactose, microcrystalline cellulose and corn starch, wherein D90 of the nifedipine is 95-135 mu m, the mass ratio of the lactose to the nifedipine is within the range of 1.8:1-2.2:1, the using amount of tween accounts for 6-9% of the total mass of a tablet core, and the preparation method of the nifedipine sustained-release tablet composition comprises the following steps:
firstly, nifedipine bulk drug is processed to the required particle size range;
and a second step of preparing an adhesive: preparing the corn starch with the prescription amount into a solution with the concentration of 2% -8%, preparing by adopting a pulp washing method, adding the Tween-80 with the prescription amount for later use, and uniformly stirring to be used as a bonding agent;
thirdly, adding nifedipine and lactose in the prescribed amount into a multifunctional fluidized bed, and granulating by using the slurry prepared in the second step;
fourthly, after finishing the granules, uniformly mixing the granules with the microcrystalline cellulose with the prescription amount, adding magnesium stearate, uniformly mixing, and tabletting by using a phi 6 circular punch die;
fifthly, film coating: and weighing the film coating powder, slowly adding the film coating powder into purified water, fully and uniformly dispersing, coating the nifedipine tablet, and increasing the weight of the coating by 3-5% to obtain the nifedipine sustained-release tablet.
2. The nifedipine sustained-release tablet composition according to claim 1, which comprises 20g of nifedipine with D90 of 95-135 μm, 805-7 g of tween-805, 36-44g of lactose, 5g of corn starch, 8-12g of microcrystalline cellulose and 1g of magnesium stearate per thousand of the tablet composition.
3. The nifedipine sustained-release tablet composition according to claim 1, which comprises 20g of nifedipine with D90 of 95-115 μm, 806 g of tween-806, 40g of lactose, 5g of corn starch, 8g of microcrystalline cellulose and 1g of magnesium stearate per thousand of the tablet composition.
4. Nifedipine sustained-release tablet composition according to claim 1, wherein the preparation process is carried out in the absence of light.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0385582A1 (en) * | 1989-02-14 | 1990-09-05 | Ethical Pharmaceuticals Limited | Nifedipine-containing pharmaceutical compositions and process for the preparation thereof |
| US5264446A (en) * | 1980-09-09 | 1993-11-23 | Bayer Aktiengesellschaft | Solid medicament formulations containing nifedipine, and processes for their preparation |
| WO2004087102A2 (en) * | 2003-03-26 | 2004-10-14 | Teva Pharmaceutical Industries Ltd. | A process for preparing a pharmaceutical active ingredient with high specific surface area |
| CN101869555A (en) * | 2009-04-21 | 2010-10-27 | 扬子江药业集团北京海燕药业有限公司 | Nifedipine controlled -release tablet and preparation technology thereof |
| CN103565769A (en) * | 2012-07-18 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN105412040A (en) * | 2015-12-14 | 2016-03-23 | 西南药业股份有限公司 | Nifedipine controlled release tablet and preparation method thereof |
| CN105920000A (en) * | 2016-06-27 | 2016-09-07 | 国药集团广东环球制药有限公司 | Nifedipine sustained release preparation and preparation method thereof |
| CN108186593A (en) * | 2018-02-06 | 2018-06-22 | 南京百思福医药科技有限公司 | A kind of Nifedipine sustained release tablets and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090104273A1 (en) * | 1999-06-22 | 2009-04-23 | Elan Pharma International Ltd. | Novel nifedipine compositions |
-
2018
- 2018-10-23 CN CN201811238357.8A patent/CN109172534B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5264446A (en) * | 1980-09-09 | 1993-11-23 | Bayer Aktiengesellschaft | Solid medicament formulations containing nifedipine, and processes for their preparation |
| EP0385582A1 (en) * | 1989-02-14 | 1990-09-05 | Ethical Pharmaceuticals Limited | Nifedipine-containing pharmaceutical compositions and process for the preparation thereof |
| WO2004087102A2 (en) * | 2003-03-26 | 2004-10-14 | Teva Pharmaceutical Industries Ltd. | A process for preparing a pharmaceutical active ingredient with high specific surface area |
| CN101869555A (en) * | 2009-04-21 | 2010-10-27 | 扬子江药业集团北京海燕药业有限公司 | Nifedipine controlled -release tablet and preparation technology thereof |
| CN103565769A (en) * | 2012-07-18 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN105412040A (en) * | 2015-12-14 | 2016-03-23 | 西南药业股份有限公司 | Nifedipine controlled release tablet and preparation method thereof |
| CN105920000A (en) * | 2016-06-27 | 2016-09-07 | 国药集团广东环球制药有限公司 | Nifedipine sustained release preparation and preparation method thereof |
| CN108186593A (en) * | 2018-02-06 | 2018-06-22 | 南京百思福医药科技有限公司 | A kind of Nifedipine sustained release tablets and preparation method thereof |
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Denomination of invention: Nifedipine sustained release tablet composition Effective date of registration: 20211025 Granted publication date: 20200807 Pledgee: Bank of China Limited Weihai Branch Pledgor: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Registration number: Y2021980010533 |