CN103845318A - Entacapone dispersible tablet - Google Patents
Entacapone dispersible tablet Download PDFInfo
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- CN103845318A CN103845318A CN201210521949.7A CN201210521949A CN103845318A CN 103845318 A CN103845318 A CN 103845318A CN 201210521949 A CN201210521949 A CN 201210521949A CN 103845318 A CN103845318 A CN 103845318A
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- entacapone
- dispersible tablet
- prescription
- lactose
- silicified microcrystalline
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Abstract
The invention relates to a pharmaceutical preparation and particularly relates to a dispersible tablet preparation containing entacapone. The preparation consists of entacapone, silicified microcrystalline cellulose, lactose, cross-linked carboxymethyl cellulose, magnesium lauryl sulfate and sodium stearyl fumarate.
Description
Technical field
The present invention relates to pharmaceutical preparation, particularly contain the dispersible tablet formulation of entacapone, the consisting of of said preparation: entacapone, silicified microcrystalline cellulose, lactose, cross-linking sodium carboxymethyl cellulose, Stepanol MG, sodium stearyl fumarate.
Background technology
Entacapone, ((E))-2-cyano group-3-(3,4-dihydroxy-5-nitrobenzophenone)-N-diethyl-2-allylamine), be catechol O-methyltransferase (COMT) inhibitor, itself and levodopa and dopa decarboxylase inhibitor combination are used for the treatment of parkinson disease (PD).Independent preparation is trade name Comtess
?and Comtan
?sell, and fixed combination (levodopa: carbidopa: entacapone: 50mg:12.5mg:200mg, 100mg:25mg:200mg and 150mg:37.5mg:200mg) is with trade name Stalevo
?sell.
When processing suffer the fluctuation of serious switch late period PD patient symptom be to pay particular attention to.Doctor is generally them and outputs separate dosage forms, and this is because the elasticity of this dosage form dosage aspect.If can obtain the dosage form conveniently taken so those patients (particularly having the patient of dysphagia) will be benefited.
In recent years, oral preparation of quick releasing development is very fast, according to statistics, and nearly 200,000,000 dollars of world's quick releasing formulation sales volume in 1996.Wherein disintegrate becomes the dispersible tablet of uniform viscosity suspension rapidly, due to its taking convenience, absorbs soon, and bioavailability high, receives people's concern day by day.The kind of this kind of dosage form also increases gradually.It is predicted Future Ten year, in all sale medicines in the world, approximately 10% will occur with novel release dosage form, and its market sale share is estimated annual growth by 1%, and this instant novel form of dispersible tablet is expected to obtain developing sooner.
Entacapone dosage form is mainly tablet, because entacapone water solublity is bad, is difficult to absorb, entacapone has been run into difficulty as the dosage form of dispersible tablet, and the present invention, through screening study, has found solution, and improved the rapid disintegrate of a kind of chance water, and drug-eluting is fast, and bioavailability is high.Take with respect to the patient Geng Yi of old man and dysphagia, mouthfeel is better simultaneously, taking convenience, and patient is easy to accept, portable novel formulation.
Summary of the invention
The invention provides a kind of pharmaceutical preparation, particularly contain the pharmaceutical preparation of entacapone, the consisting of of said preparation: entacapone, silicified microcrystalline cellulose, lactose, cross-linking sodium carboxymethyl cellulose, Stepanol MG, sodium stearyl fumarate, 50% alcoholic solution.
This pharmaceutical preparation chamber tablet form, particularly dispersible tablet form, described dispersible tablet is that tablet is put in appropriate water, makes it to disperse disintegrate, the dosage form of then together taking with water.The present invention, through screening, has found the particularly advantageous dispersible tablet prescription of entacapone.
Therefore, the invention provides entacapone dispersible tablet formulation, wherein contain active constituents of medicine entacapone and the medicine acceptable carrier that is applicable to preparing dispersible tablet, the wherein said drug acceptable carrier that is applicable to preparing dispersible tablet is selected from following composition: silicified microcrystalline cellulose, lactose, cross-linked carboxymethyl cellulose, Stepanol MG, starch, sodium stearyl fumarate, Pulvis Talci etc.Preferred composition is silicified microcrystalline cellulose, cross-linking sodium carboxymethyl cellulose, and Stepanol MG, sodium stearyl fumarate, 50% alcoholic solution is wetting agent.
Therefore, entacapone dispersible tablet formulation of the present invention is preferably write out a prescription composed as follows:
| Entacapone | 100-400g |
| Silicified microcrystalline cellulose | 500-700g |
| Lactose | 250-350g |
| Cross-linking sodium carboxymethyl cellulose | 80-160g |
| Stepanol MG | 5-30g |
| Sodium stearyl fumarate | 2-100g |
| 50% ethanol | 1-100ml |
| Make | 1000 |
Most preferred prescription is as follows
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 55.39g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% ethanol | In right amount |
| Make | 1000 |
The present invention also comprises the preparation method of entacapone dispersible tablet, its basic step adopts galenic pharmacy routine techniques, as the carrier of active component and medicine is mixed, tabletting etc., 50% alcoholic solution is wetting agent, and consumption when use is so that make and be applicable to the granule of tabletting and be as the criterion, according to routine, use amount be between the 0.5%-5% of inventory for suitable, be preferably 1%.
Specifically can adopt following methods:
The preparation of 1 supplementary material and processing:
By entacapone disperseed that 200 mesh sieves are for subsequent use, silicified microcrystalline cellulose, cross-linking sodium carboxymethyl cellulose, that lactose is crossed 100 mesh sieves is for subsequent use.
2 weigh and mix:
2.1 take respectively above-mentioned supplementary material according to recipe quantity through the double calculating inventory of checking.
2.2 by above-mentioned supplementary material by the equivalent method mix homogeneously that progressively increases
3 granulate:
3.1 soft materials processed: with 50% alcoholic solution soft material processed, granulate with 20 order nylon wires, the granule making should lack particulate, neat without rectangular.
3.2 is dry: the temperature of 55 ± 2 DEG C, in drying baker inner drying 5-7 hour.
3.3 processing of dry grain before tabletting:
Granulate: in pelletization, have excessive granule, the granulate that need to sieve, makes into the single-size that is applicable to tabletting; Sieve and select 16 mesh sieve granulate.
3.4 add lubricant, and mix homogeneously is placed in hermetic container tabletting after the assay was approved.
4 measure granule content, calculate sheet weight:
Sampling is pressed quality standard and is measured granule content, and theoretical sheet is heavily 0.9g.
5 tablettings: according to the actual sheet weight of result of calculation gained, regulate tablet machine tabletting, put into hermetic container sampling check hardness after completing.
6 inspections of semifinished product: pack after the assay was approved by quality standard requirement.
7 pack according to the requirement of product, and after packaging, warehouse-in, can dispatch from the factory after the assay was approved according to quality standard.
Entacapone dispersible tablet prescription of the present invention obtains through screening, and its screening process is as follows:
Prescription screening
In 1 prescription screening process, use silicified microcrystalline cellulose in order to reach good dispersing uniformity filler, disintegrating agent conventional carboxymethyl starch sodium on probation, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone etc. have reached more satisfied stripping curve: be the screening of several supplementary product consumptions below:
Prescription 1
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Carboxymethyl starch sodium | 55.39g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% alcoholic solution | In right amount |
| Make | 1000 |
Prescription 2
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Crospolyvinylpyrrolidone | 55.39g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% alcoholic solution | In right amount |
| Make | 1000 |
Prescription 3
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 55.39g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% alcoholic solution | In right amount |
| Make | 1000 |
Prescription 4
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 55.39g |
| Polyvidone | 4.64g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% alcoholic solution | In right amount |
| Make | 1000 |
Adopt HPLC to get this product according to dissolution method (two annex XC the second methods of Chinese Pharmacopoeia version in 2000), taking water 900ml as solvent, rotating speed is per minute 50 to turn, got a little at 2,4,7,10,15 minutes respectively, precision measures and in filtrate 5ml → 50ml measuring bottle, is diluted with water to scale and shakes up, and mends dissolution fluid 5ml, according to spectrophotography (annex IV A), wavelength place at 274nm measures trap, the results are shown in Table 1
Table 1 stripping curve measurement result
| Prescription number | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| 2 minutes | 25.4% | 26.0% | 37.0% | 30.7% |
| 4 minutes | 40.3% | 52.1% | 62.8% | 50.7% |
| 10 minutes | 75.2% | 79.4% | 93.7% | 77.0% |
| 15 minutes | 90.3% | 91.8% | 99.5% | 96.7% |
| Hardness | 11.25kg | 10.60kg | 11.78kg | 10.75kg |
| Dispersing uniformity | 1 minute 40 seconds | 2 minutes 10 seconds | 1 minute 05 second | 2 minutes 24 seconds |
Shown by above result of the test: what prescription 1-4 dispersing uniformity was best is prescription 3 is 1 point of 05 second and it is 93.7% the highest at the dissolution of 10 minutes, and the dispersing uniformity of all the other 3 prescriptions and stripping curve are all not as 3 ideals of writing out a prescription; Still select to write out a prescription and 3 amplify, its lot number is 030505,030507,030509.
2 factors affecting stability tests:
(1) strong illumination test:
Get 030505 batch of entacapone dispersible tablet and be placed in glass dish, place 10 days under the illumination of 4500LX ± 100LX, detect in sampling in 0,5,10 day, testing result is in table 2:
Table 2 strong illumination result of the test
* 1: entacapone Z-isomer 2:3,4-dihydroxy-5-nitrobenzaldehyde
(2) hot test:
Get 030505 batch of entacapone dispersible tablet and be placed in glass dish, place 10 days in the calorstat of 60 DEG C, detect in sampling in 0,5,10 day, testing result is in table 3:
60 DEG C of thimble test results of table 3
* 1: entacapone Z-isomer 2:3,4-dihydroxy-5-nitrobenzaldehyde
(3) high wet test:
Get 030505 batch of entacapone dispersible tablet and be placed in glass dish, respectively at relative humidity 75%(NaCl saturated solution), 92.5%(KNO3 saturated solution) calorstat in place 10 days, detect in sampling in 0,5,10 day, testing result is in table 4 and table 5:
Table 4 75% high humidity stability test result
* 1: entacapone Z-isomer 2:3,4-dihydroxy-5-nitrobenzaldehyde
Table 5 92.5% high humidity stability test result
* 1: entacapone Z-isomer 2:3,4-dihydroxy-5-nitrobenzaldehyde
Above experimental result shows, this product is all stable under the condition of illumination, 60 DEG C of high temperature and high humidity.
Pharmaceutical preparation of the present invention, has overcome defect of the prior art, prepares stablely, and safety, absorbs soon, dissolves soon, prepares simple novel drugs.
Detailed description of the invention
The present invention is described further by the following examples, but not as limitation of the present invention.
Embodiment 1
| Entacapone | 200g |
| Silicified microcrystalline cellulose | 400g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 55.39g |
| Stepanol MG | 3.32g |
| Sodium stearyl fumarate | 4.64g |
| 50% ethanol | In right amount |
| Make | 1000 |
The present invention also comprises the preparation method of entacapone dispersible tablet, and its basic step adopts galenic pharmacy routine techniques, as the carrier of active component and medicine is mixed, and tabletting etc.
Specifically can adopt following methods:
The preparation of 1 supplementary material and processing:
By entacapone disperseed that 200 mesh sieves are for subsequent use, silicified microcrystalline cellulose, lactose, that cross-linking sodium carboxymethyl cellulose is crossed 100 mesh sieves is for subsequent use.
2 weigh and mix:
2.1 take respectively above-mentioned supplementary material according to recipe quantity through the double calculating inventory of checking.
2.2 by above-mentioned supplementary material by the equivalent method mix homogeneously that progressively increases
3 granulate:
3.1 soft materials processed: with 50% alcoholic solution soft material processed, granulate with 20 order nylon wires, the granule making should lack particulate, neat without rectangular.
3.2 is dry: the temperature of 55 ± 2 DEG C, in drying baker inner drying 5-7 hour.
3.3 processing of dry grain before tabletting:
Granulate: in pelletization, have excessive granule, the granulate that need to sieve, makes into the single-size that is applicable to tabletting; Sieve and select 16 mesh sieve granulate.
3.4 add lubricant, and mix homogeneously is placed in hermetic container tabletting after the assay was approved.
4 measure granule content, calculate sheet weight:
Sampling is pressed quality standard and is measured granule content, and theoretical sheet is heavily 0.9g.
5 tablettings: according to the actual sheet weight of result of calculation gained, regulate tablet machine tabletting, put into hermetic container sampling check hardness after completing.
6 inspections of semifinished product: pack after the assay was approved by quality standard requirement.
7 pack according to the requirement of product, and after packaging, warehouse-in, can dispatch from the factory after the assay was approved according to quality standard.
Embodiment 2
| Entacapone | 100g |
| Silicified microcrystalline cellulose | 200g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 27.69g |
| Stepanol MG | 1.66g |
| Sodium stearyl fumarate | 2.32g |
| 50% ethanol | In right amount |
| Make | 1000 |
Preparation method is with embodiment 1
Embodiment 3
| Entacapone | 400g |
| Silicified microcrystalline cellulose | 800g |
| Lactose | 200g |
| Cross-linking sodium carboxymethyl cellulose | 110.78g |
| Stepanol MG | 6.64g |
| Sodium stearyl fumarate | 9.28g |
| 50% ethanol | In right amount |
| Make | 1000 |
Preparation method is with embodiment 1.
Claims (2)
1. a dispersible tablet for entacapone, the prescription that it is characterized in that making 1000 is composed as follows:
Entacapone 100-400g
Silicified microcrystalline cellulose 500-700g
Lactose 250-350g
Cross-linked carboxymethyl cellulose 80-160g
Stepanol MG 5-30g
Sodium stearyl fumarate 2-100g
50% alcoholic solution 1-100ml.
2. dispersible tablet according to claim 1, the prescription that it is characterized in that making 1000 is composed as follows:
Entacapone 200g
Silicified microcrystalline cellulose 400g
Lactose 200g
Cross-linked carboxymethyl cellulose 55.39g
Stepanol MG 3.32g
Sodium stearyl fumarate 4.64g
50% alcoholic solution 1-100ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210521949.7A CN103845318A (en) | 2012-12-07 | 2012-12-07 | Entacapone dispersible tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210521949.7A CN103845318A (en) | 2012-12-07 | 2012-12-07 | Entacapone dispersible tablet |
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| Publication Number | Publication Date |
|---|---|
| CN103845318A true CN103845318A (en) | 2014-06-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210521949.7A Pending CN103845318A (en) | 2012-12-07 | 2012-12-07 | Entacapone dispersible tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103845318A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106236718A (en) * | 2016-08-29 | 2016-12-21 | 海南通用康力制药有限公司 | A kind of pharmaceutical composition of Tedizolid Phosphate and preparation method thereof |
| CN106236720A (en) * | 2016-08-29 | 2016-12-21 | 海南通用康力制药有限公司 | A kind of pharmaceutical composition of entacapone and preparation method thereof |
| CN110441421A (en) * | 2019-08-02 | 2019-11-12 | 聊城高新生物技术有限公司 | A kind of method of high effective liquid chromatography for measuring Entacapone tablet dissolution |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184483A (en) * | 2005-06-08 | 2008-05-21 | 奥赖恩公司 | An entacapone-containging oral dosage form |
| WO2010134074A1 (en) * | 2009-05-19 | 2010-11-25 | Neuroderm Ltd | Compositions for continuous administration of dopa decarboxylase inhibitors |
-
2012
- 2012-12-07 CN CN201210521949.7A patent/CN103845318A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184483A (en) * | 2005-06-08 | 2008-05-21 | 奥赖恩公司 | An entacapone-containging oral dosage form |
| WO2010134074A1 (en) * | 2009-05-19 | 2010-11-25 | Neuroderm Ltd | Compositions for continuous administration of dopa decarboxylase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| 曹德英等: "《药物剂型与制剂设计》", 31 May 2009 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106236718A (en) * | 2016-08-29 | 2016-12-21 | 海南通用康力制药有限公司 | A kind of pharmaceutical composition of Tedizolid Phosphate and preparation method thereof |
| CN106236720A (en) * | 2016-08-29 | 2016-12-21 | 海南通用康力制药有限公司 | A kind of pharmaceutical composition of entacapone and preparation method thereof |
| CN110441421A (en) * | 2019-08-02 | 2019-11-12 | 聊城高新生物技术有限公司 | A kind of method of high effective liquid chromatography for measuring Entacapone tablet dissolution |
| CN110441421B (en) * | 2019-08-02 | 2022-09-09 | 聊城高新生物技术有限公司 | Method for determining dissolution rate of entacapone tablets by high performance liquid chromatography |
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Application publication date: 20140611 |
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