CN112121023A - Fenofibrate tablet composition - Google Patents
Fenofibrate tablet composition Download PDFInfo
- Publication number
- CN112121023A CN112121023A CN202011054024.7A CN202011054024A CN112121023A CN 112121023 A CN112121023 A CN 112121023A CN 202011054024 A CN202011054024 A CN 202011054024A CN 112121023 A CN112121023 A CN 112121023A
- Authority
- CN
- China
- Prior art keywords
- fenofibrate
- tablet composition
- polyethylene glycol
- polysorbate
- magnesium stearate
- 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.)
- Withdrawn
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- 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
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Abstract
The invention relates to a fenofibrate composition, and belongs to the technical field of pharmaceutical preparations. The technical scheme of the invention is as follows: a fenofibrate tablet composition, comprising per 1000 tablets: d90 is 6-8 micron fenofibrate 1g, polyethylene glycol 60008-18 g, calcium dihydrogen phosphate 5-14g, microcrystalline cellulose 30-50g, hydroxypropyl cellulose E520-30 g, polysorbate-808-16 g, and magnesium stearate 1-2 g. The invention provides a fenofibrate tablet composition, which overcomes the defect that the dissolution rate of the fenofibrate tablet composition is low in the storage process, and provides a fenofibrate tablet composition with stable quality.
Description
Technical Field
The invention relates to a fenofibrate composition, and belongs to the technical field of pharmaceutical preparations.
Background
Fenofibrate tablet is first applied to clinic in 1975, is mainly used for treating hyperlipidemia with unsatisfactory adult diet control therapy, is one of the first-choice medicines for reducing triglyceride, has obvious effect of reducing triglyceride and mixed hyperlipidemia compared with cholesterol, can reduce the level of hematuria, has good effect on treating type 2 diabetes and metabolic syndrome, is one of the most commonly used fibrate medicines, and has good effect and tolerance.
According to the biopharmaceutical classification system, fenofibrate belongs to the classical class ii drug. Due to the difficult solubility and the poor dissolution rate of fenofibrate, the bioavailability of fenofibrate is low, and the oral bioavailability of fenofibrate is only 35%. In order to improve the bioavailability, the Chinese patent 02153536.1 is to crush fenofibrate to be less than 5 microns and then granulate and tabletting; 99801884.5 patent, pulverizing fenofibrate to less than 20 μm, granulating and tabletting; 200480028731.1 patent micronizes fenofibrate and adds surfactant to the formulation to increase dissolution.
Experiments show that after micronization, the dissolution rate of fenofibrate can be improved by adding a surfactant into the formula, but stability experiments show that the dissolution rate of the tablet is reduced along with the prolonging of the storage time. Analysis shows that the dissolution of the aggregated larger fenofibrate particles is not easy as the dissolution of the fenofibrate particles in 0 day, so that the dissolution of the fenofibrate tablets is reduced, and the clinical use effect is influenced.
Disclosure of Invention
The purpose of the invention is as follows: the problem of dissolution reduction of the micronized fenofibrate tablets in the storage process is solved.
The technical scheme of the invention is as follows: a fenofibrate tablet composition, comprising per 1000 tablets: d90 is 6-8 micron fenofibrate 1g, polyethylene glycol 60008-18 g, calcium dihydrogen phosphate 5-14g, microcrystalline cellulose 30-50g, hydroxypropyl cellulose E520-30 g, polysorbate-808-16 g, and magnesium stearate 1-2 g.
In the technical scheme of the invention, the introduction of the polyethylene glycol and the monocalcium phosphate plays an active role in the stability of the micro powder fenofibrate tablet composition, and the problem of dissolution rate reduction in the storage process is solved.
The contents of polyethylene glycol and monocalcium phosphate are too low, and the stability of the dissolution rate cannot reach the expected purpose; the dissolution in 0 day is affected by the fact that the hardness of the tablet is increased due to too high content of polyethylene glycol; the high content of calcium dihydrogen phosphate affects the dissolution stability in the storage process.
The preferred technical scheme of the invention is as follows: a fenofibrate tablet composition, comprising per 1000 tablets: d90 is 6-8 micron fenofibrate 1g, polyethylene glycol 600012-15 g, calcium dihydrogen phosphate 7-10.6g, microcrystalline cellulose 40-48g, hydroxypropyl cellulose E522-28 g, polysorbate-8010-14 g and magnesium stearate 1.5 g.
The preferred technical scheme of the invention is as follows: a fenofibrate tablet composition, comprising per 1000 tablets: d90 is 7-micron fenofibrate 1g, polyethylene glycol 600013 g, calcium dihydrogen phosphate 10.5g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g, polysorbate-8012 g, and magnesium stearate 1.5 g.
The preparation method of the fenofibrate tablet composition comprises the following steps:
step 1, grinding the fenofibrate raw material medicine to a required particle size, and sieving other solid auxiliary materials by a 80-mesh sieve;
step 2, uniformly mixing fenofibrate, polysorbate-80, monocalcium phosphate and polyethylene glycol according to the prescription amount, and then uniformly mixing the mixture with microcrystalline cellulose and hydroxypropyl cellulose E5 according to the prescription amount in a fluidized bed;
step 3, spraying 30-45% ethanol water solution to the granules obtained in the step 2, and granulating;
step 4, granulating and drying at 60 ℃;
and 5, adding magnesium stearate in the prescription amount, and tabletting.
According to the preparation method, fenofibrate is firstly uniformly mixed with polysorbate-80, monocalcium phosphate and polyethylene glycol, and then is uniformly mixed with other auxiliary materials for granulation, so that the dissolution rate and the stability of the dissolution rate of the tablet can be improved, and a slight positivity effect is achieved; by adopting a mode of spraying 30-45% of ethanol water solution, utilizing the viscosity of polyethylene glycol and microcrystalline cellulose for granulation, preferentially using 35-40% of ethanol water solution, the hardness of the tablet can be reduced, and the dissolution rate of the tablet can be improved.
If the granulation is carried out by spraying with water or an ethanol solution having a concentration of less than 30%, the hardness of the resulting tablet is too high to affect the dissolution of the drug. If the concentration of the ethanol aqueous solution is too high, the production safety control is not facilitated. Therefore, the 30-45% ethanol water solution is selected to be sprayed for granulation.
Has the advantages that: the invention provides a fenofibrate tablet composition, which meets the requirements of pharmacopoeia and can reduce adverse reactions of patients after administration.
Example 1. D90 is 6 micron fenofibrate 1g, polyethylene glycol 60008 g, calcium dihydrogen phosphate 5g, microcrystalline cellulose 50g, hydroxypropyl cellulose E520 g, polysorbate-808 g, magnesium stearate 1g, and 1000 tablets are prepared according to the preparation method of the technical scheme.
Example 2. D90 is 8 micron fenofibrate 1g, polyethylene glycol 600018 g, calcium dihydrogen phosphate 14g, microcrystalline cellulose 30g, hydroxypropyl cellulose E530 g, polysorbate-8016 g, and magnesium stearate 2g, and 1000 tablets are prepared according to the preparation method of the technical scheme.
Example 3. D90 is 7 micron fenofibrate 1g, polyethylene glycol 600013 g, calcium dihydrogen phosphate 10.5g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g, polysorbate-8012 g, magnesium stearate 1.5g, and 1000 tablets are prepared according to the preparation method of the technical scheme.
Comparative example 1. preparation of 1000 tablets was carried out in the same manner as in example 3.
Step 1, grinding the fenofibrate raw material medicine to a required particle size, and sieving other solid auxiliary materials by a 80-mesh sieve;
and 2, placing the fenofibrate, the polysorbate-80, the polyethylene glycol, the monocalcium phosphate, the microcrystalline cellulose and the hydroxypropyl cellulose E5 in the formula amount into a fluidized bed and uniformly mixing.
And 3, spraying 30-45% of ethanol water solution to the granules obtained in the step 2, and granulating.
And 4, finishing the granules and drying at 60 ℃.
And 5, adding magnesium stearate in the prescription amount, and tabletting.
Comparative example 2 adjustment with reference to the recipe of example 3
D90 is 7-micron fenofibrate 1g, polyethylene glycol 600022 g, monocalcium phosphate 20g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g, polysorbate-8012 g and magnesium stearate 1.5g, and 1000 tablets are prepared according to the preparation method of the technical scheme.
Comparative example 3 adjustment with reference to the recipe of example 3
D90 is 7-micron fenofibrate 1g, polyethylene glycol 60005 g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g g, polysorbate-8012 g and magnesium stearate 1.5g, and 1000 tablets are prepared by the preparation method according to the technical scheme.
Comparative example 4 adjustment with reference to the recipe of example 3
D90 is 7 μm fenofibrate 1g, calcium dihydrogen phosphate 10.5g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g, polysorbate 8012 g, and magnesium stearate 1.5g
Comparative example 5. the formulation was the same as in example 3, and 1000 tablets were prepared by spraying purified water and granulating as described in the specification.
Test example 1 accelerated stability test
100 tablets of the products of examples 1 to 3 and comparative examples 1 to 5 were respectively taken, respectively packaged by aluminum-plastic, placed in a constant temperature and humidity chamber at 40 ℃ and relative humidity of 75% RH, and taken out at the end of 3 rd month and at the end of 6 th month respectively to measure the dissolution rate.
Dissolution of the products of examples 1-3, comparative examples 1-5 was measured in pH1.0 medium (0.025 mol/SDS (sodium dodecyl sulphate)) according to dissolution determination method second method, paddle method, 900ml dissolution medium set as defined in pharmacopoeia appendix XC, version 2015, rotation speed 75 r/min, temperature setting (37. + -. 0.5 ℃) and the data reported in Table 1.
TABLE 1 summary of dissolution data at 60min in hydrochloric acid solution medium pH1.0
Table 1 the data illustrates: according to the technical scheme, proper amounts of polyethylene glycol 6000 and monocalcium phosphate are added, so that the dissolution rate of the fenofibrate tablets is prevented from being reduced in the storage process. Provides a product with stable quality for clinic.
Claims (4)
1. A fenofibrate tablet composition, which contains per 1000 tablets: d90 is 6-8 micron fenofibrate 1g, polyethylene glycol 60008-18 g, calcium dihydrogen phosphate 5-14g, microcrystalline cellulose 30-50g, hydroxypropyl cellulose E520-30 g, polysorbate-808-16 g, and magnesium stearate 1-2 g.
2. The fenofibrate tablet composition of claim 1, comprising per 1000 tablets: d90 is 6-8 micron fenofibrate 1g, polyethylene glycol 600012-15 g, calcium dihydrogen phosphate 7-10.6g, microcrystalline cellulose 40-48g, hydroxypropyl cellulose E522-28 g, polysorbate-8010-14 g and magnesium stearate 1.5 g.
3. The fenofibrate tablet composition of claim 1, comprising per 1000 tablets: d90 is 7-micron fenofibrate 1g, polyethylene glycol 600013 g, calcium dihydrogen phosphate 10.5g, microcrystalline cellulose 45g, hydroxypropyl cellulose E526 g, polysorbate-8012 g, and magnesium stearate 1.5 g.
4. A method of preparing a fenofibrate tablet composition according to claim 1, comprising the steps of:
step 1, grinding the fenofibrate raw material medicine to a required particle size, and sieving other solid auxiliary materials by a 80-mesh sieve;
step 2, uniformly mixing fenofibrate, polysorbate-80, monocalcium phosphate and polyethylene glycol according to the prescription amount, and then uniformly mixing the mixture with microcrystalline cellulose and hydroxypropyl cellulose E5 according to the prescription amount in a fluidized bed;
step 3, spraying 30-45% ethanol water solution to the granules obtained in the step 2, and granulating;
step 4, granulating and drying at 60 ℃;
and 5, adding magnesium stearate in the prescription amount, and tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011054024.7A CN112121023A (en) | 2020-09-30 | 2020-09-30 | Fenofibrate tablet composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011054024.7A CN112121023A (en) | 2020-09-30 | 2020-09-30 | Fenofibrate tablet composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112121023A true CN112121023A (en) | 2020-12-25 |
Family
ID=73844839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011054024.7A Withdrawn CN112121023A (en) | 2020-09-30 | 2020-09-30 | Fenofibrate tablet composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112121023A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1360499A (en) * | 1999-07-09 | 2002-07-24 | 埃迪克埃迪法姆药品实验室 | Pharmaceutical composition contg. fenofibrate and preparation method |
| US20070015834A1 (en) * | 2005-07-18 | 2007-01-18 | Moshe Flashner-Barak | Formulations of fenofibrate containing PEG/Poloxamer |
| CN101594850A (en) * | 2006-12-21 | 2009-12-02 | 兰贝克赛实验室有限公司 | Antilipidemic pharmaceutical compositions and and preparation method thereof |
| CN104352466A (en) * | 2014-11-17 | 2015-02-18 | 辰欣药业股份有限公司 | Fenofibrate composition and preparation thereof |
-
2020
- 2020-09-30 CN CN202011054024.7A patent/CN112121023A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1360499A (en) * | 1999-07-09 | 2002-07-24 | 埃迪克埃迪法姆药品实验室 | Pharmaceutical composition contg. fenofibrate and preparation method |
| US20070015834A1 (en) * | 2005-07-18 | 2007-01-18 | Moshe Flashner-Barak | Formulations of fenofibrate containing PEG/Poloxamer |
| CN101594850A (en) * | 2006-12-21 | 2009-12-02 | 兰贝克赛实验室有限公司 | Antilipidemic pharmaceutical compositions and and preparation method thereof |
| CN104352466A (en) * | 2014-11-17 | 2015-02-18 | 辰欣药业股份有限公司 | Fenofibrate composition and preparation thereof |
Non-Patent Citations (2)
| Title |
|---|
| SIDDHARTH S CHACHAD等: "Comparison of pharmacokinetics of two fenofibrate tablet formulations in healthy human subjects", 《CLIN THER.》 * |
| 任秀华等: "非诺贝特固体分散片的试制", 《中国医药工业杂志》 * |
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| PB01 | Publication | ||
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| WW01 | Invention patent application withdrawn after publication | ||
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Application publication date: 20201225 |