CN105030707A - Method for preparing clotrimazole buccal tablets on basis of all-powder direct pressing of modified glucose - Google Patents
Method for preparing clotrimazole buccal tablets on basis of all-powder direct pressing of modified glucose Download PDFInfo
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- CN105030707A CN105030707A CN201510401211.0A CN201510401211A CN105030707A CN 105030707 A CN105030707 A CN 105030707A CN 201510401211 A CN201510401211 A CN 201510401211A CN 105030707 A CN105030707 A CN 105030707A
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Abstract
The invention belongs to the technical field of pharmaceuticals and relates to a method for preparing clotrimazole buccal tablets on basis of all-powder direct pressing of modified glucose. The clotrimazole buccal tablets are composed of the modified glucose, filler, lubricant and disintegrant. The modified glucose is prepared from dextrose monohydrate and binder; the binder is povidone K30. The percentage by weight of the povidone K30 is 0.1% to 0.1% of that of the modified glucose, preferably 0.1% to 0.5% and more preferably 0.1% to 0.3%. Water and ethyl alcohol are used as solvents for the povidone K30 and are subjected to granulating, drying and size stabilizing with the dextrose monohydrate, and water content of the modified glucose is 0.5% to 3%. A single dose of the clotrimazole buccal tablets contains 10mg of an active ingredient, clotrimazole.
Description
Technical field
The invention belongs to medical art, relate to a kind of method adopting the full powder direct pressure closing of modified glucose to prepare clotrimazole buccal tablet.
Background technology
Oral candidiasis (oropharyngealcandidiasis, OPC) is acute, the subacute or chronic fungal infectious disease of oral mucosa that Candida sense causes.Its clinical symptoms comprises diffuse erythema and white curdy patch or shows as buccal mucosa, throat, tongue, and the speckle of gingival surface discreteness pathological changes.Along with 17-hydroxy-11-dehydrocorticosterone, broad ectrum antibiotic and other immunosuppressant widely using clinically, in addition the appearance of acquired immune deficiency syndrome (AIDS) and the development of organ transplantation, there is dysbacteriosis or immunity reduction, and making internal organs, skin, mucosa fungal infection person increasing, the incidence rate of Oral mucous Candidiasis is also corresponding to be increased.
Pyrroles's lopps antifungal drug: pyrroles's lopps pharmaceutical pack draws together imidazoles and antifungal drug in triazole class, its effect is all relevant with the synthesis of ergosterol in Antifungi body, and then destroys the integrity of fungal cell membrane, reaches antifungal effect.Clotrimazole belongs to pyroles antifungal agent, has broad-spectrum antifungal activity, has good inhibitory action to Candida.
Clotrimazole is oral gastrointestinal reaction, abnormal liver function and granulocytopenia etc., therefore does not generally adopt.Buccal tablet can topical, makes medicine by mucosal absorption, avoids the liver first-pass effect of medicine, improve bioavailability, extend action time, in addition compared with general tablet, buccal tablet also have absorb fast, effect rapidly, untoward reaction is few, patient compliance good, the advantage such as removable if desired.
Clotrimazole buccal tablet goes on the market abroad.Employ glucose conjugate in prescription, domestic at present still do not have import and production, and my company have employed glucose as filler.Clotrimazole buccal tablet is small dose drug, and uniformity of dosage units is an important inspection target.But in prescription process, find the non-constant of homogeneity preparing tablet, repeatability is also more unstable, causes differ greatly disintegration, causes the relative standard deviation of stripping curve larger simultaneously.Find that in glucose, moisture is comparatively obvious on the impact of prescription through further studying, it causes grain density uneven, tabletting lack of homogeneity.Adopt special preparation process to carry out modification to glucose in the present invention, this modified glucose is in physicochemical property, and the preparation of especially applicable clotrimazole buccal tablet, investigates homogeneity after tabletting and compressibility is good, and In Vitro Dissolution uniformity also meets the requirements, good mouthfeel.
Summary of the invention
The object of this invention is to provide a kind of method preparing clotrimazole buccal tablet based on the full powder direct pressure closing of modified glucose.Many experimental results finds, adopt modified glucose good as prescription compressibility after the full pressed powder of filler, repeatability and the homogeneity of clotrimazole buccal tablet are improved very well, and mouthfeel keeps good.
The present invention is as follows for the technical scheme realizing above-mentioned purpose: this clotrimazole buccal tablet, and the percentage ratio that the modified glucose in this buccal tablet accounts for sheet heavy is: 60% ~ 95%, is preferably 70% ~ 90%, is more preferably 80% ~ 90%.
Described clotrimazole buccal tablet also comprises the disintegrating agent that one or more are selected from carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose and polyvinylpolypyrrolidone, is preferably cross-linking sodium carboxymethyl cellulose; It is 1% ~ 10% that described disintegrating agent accounts for the heavy percentage ratio of sheet, is preferably 2% ~ 8%, is more preferably 2% ~ 4%.
Described clotrimazole buccal tablet can also comprise another kind of or the multiple filler being selected from starch, mannitol, calcium sulphate dihydrate and microcrystalline Cellulose, is preferably microcrystalline Cellulose; It is 1% ~ 10% that described filler accounts for the heavy percentage ratio of sheet, is preferably 2% ~ 8%, is more preferably 4% ~ 6%.
Described clotrimazole buccal tablet adopts modified glucose to be by Dextrose Monohydrate and binding agent are prepared into soft material, after soft material granulate, dry the method for granulate again, binding agent wherein can also be that one or both are selected from the binding agent of hydroxypropyl emthylcellulose and polyvidone, is preferably PVP K30.The percentage ratio of shared modified glucose is 0.10% ~ 0.15%, is preferably 0.1% ~ 0.5%, is more preferably 0.1 ~ 0.3%.
Described clotrimazole buccal tablet can also comprise the lubricant that one or more are selected from hydrogenated vegetable oil, Macrogol 4000, polyethylene glycol 6000, sodium laurylsulfate, stearic acid and magnesium stearate, is preferably magnesium stearate; It is 1% ~ 10% that described lubricant accounts for the heavy percentage ratio of sheet, is preferably 1% ~ 3%.
Present invention also offers the preparation method of described clotrimazole buccal tablet, this preparation method comprises the following steps:
(1) supplementary material pre-treatment: glucose pulverized 80 eye mesh screens, for subsequent use.Microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate cross 60 mesh sieves, for subsequent use.
(2) modified glucose preparation: by appropriate Dextrose Monohydrate, the aqueous solution adding 3% PVP K30 is granulated.After granulation terminates, at 40 ~ 60 DEG C of temperature, carry out drying, be dried to moisture and be less than 1%.
Granulate: by dried granule 16-24 eye mesh screen granulate.
(3) recipe quantity modified glucose and recipe quantity clotrimazole, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose Homogeneous phase mixing are got in mixing,
(4) always mix: add magnesium stearate again and drop into total mixed machine mixing 10min.The heavy scope of tabletting sheet is calculated according to intermediate quality standard.
(5) tabletting: carry out tabletting at DP30A type single punch tablet machine, rotating speed 20 ~ 30rpm, hardness is about 10 ~ 18kgf.
Clotrimazole specification of the present invention is 10mg, adopt this method to carry out modification to glucose, by the further screening of prescription and optimization, make the quality of product more stable, controlled, obtained clotrimazole granule compressibility improves, and dissolution and the homogeneity of tablet are also improved very well.Clinical test results shows: clotrimazole buccal tablet 10mg/ sheet, slowly dissolves, one day 5 times in mouth, one time 1, be treatment oral candidiasis effectively and the method for safety.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further described in detail, the embodiment provided only in order to illustrate the present invention, instead of in order to limit the scope of the invention.
Embodiment 1
Clotrimazole 10g
Modified glucose 830g
Microcrystalline Cellulose 50g
Cross-linking sodium carboxymethyl cellulose 100g
PVP K30 1.3g
Magnesium stearate 10g
Take the modified glucose after recipe quantity clotrimazole and granulate, after the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, then add magnesium stearate always mixed machine mixing 10min.Tabletting: carry out tabletting by the heavy scope of sheet at DP30A type single punch tablet machine, rotating speed 10 ~ 12rpm, hardness is about 8 ~ 15kgf.
Embodiment 2
Clotrimazole 10g
Glucose 830g
Microcrystalline Cellulose 50g
Cross-linking sodium carboxymethyl cellulose 100g
PVP K30 1.3g
Magnesium stearate 20g
Take the modified glucose after recipe quantity clotrimazole and granulate, after the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, then add magnesium stearate always mixed machine mixing 10min.Tabletting: carry out tabletting by the heavy scope of sheet at DP30A type single punch tablet machine, rotating speed 10 ~ 12rpm, hardness is about 8 ~ 15kgf.
Embodiment 3
Clotrimazole 10g
Modified glucose 830g
Microcrystalline Cellulose 100g
Cross-linking sodium carboxymethyl cellulose 50g
PVP K30 2.5g
Magnesium stearate 10g
Take the modified glucose after recipe quantity clotrimazole and granulate, after the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, then add magnesium stearate always mixed machine mixing 10min.Tabletting: carry out tabletting by the heavy scope of sheet at DP30A type single punch tablet machine, rotating speed 10 ~ 12rpm, hardness is about 8 ~ 15kgf.
Embodiment 4
The further optimization of prescription: in order to adjust rate of release further, intends the consumption adjusting disintegrating agent and filler on the basis of prescription 1.
Clotrimazole 10g
Modified glucose 780g
Microcrystalline Cellulose 100g
Cross-linking sodium carboxymethyl cellulose 100g
PVP K30 5g
Magnesium stearate 20g
Take the modified glucose after recipe quantity clotrimazole and granulate, after the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, then add magnesium stearate always mixed machine mixing 10min.Tabletting: carry out tabletting by the heavy scope of sheet at DP30A type single punch tablet machine, rotating speed 30 ~ 40rpm, hardness is about 8 ~ 15kgf.
Embodiment 5
Clotrimazole 10g
Modified glucose 880g
Microcrystalline Cellulose 50g
Cross-linking sodium carboxymethyl cellulose 100g
PVP K30 5g
Magnesium stearate 15g
Embodiment 6
Take the modified glucose after recipe quantity clotrimazole and granulate, after the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, then add magnesium stearate always mixed machine mixing 10min.Tabletting: carry out tabletting by the heavy scope of sheet at DP30A type single punch tablet machine, rotating speed 10 ~ 12rpm, hardness is about 8 ~ 15kgf.
Carry out scale-up according to the method recorded in embodiment 2, each three batches of each specification (150501,150502,150503), often criticizes 5000.
Table 1 lab scale amplifies sample survey result
Table 2. lab scale amplifies sample effects factorial experiments result
Each sample is placed 10 days respectively under high temperature (60 DEG C and 40 DEG C), high humidity (RH92.5% and 75%), illumination (4500 ± 500LX) condition, in sampling in the 5th day, the 10th day, investigate the change of sample appearance character, content and dissolution, and compare with 0 day sample result.Result is as shown in table 2.Under influence factor's experimental condition, the equal leading indicator of the character of clotrimazole buccal tablet, content, dissolution is without significant change.
Claims (6)
1. a clotrimazole buccal tablet, is made up of modified glucose, filler, lubricant and disintegrating agent, adopts direct compression of full-powder preparation.
2. institute comprises modified glucose in clotrimazole buccal tablet is according to claim 1 be prepared from by Dextrose Monohydrate and binding agent.
3. binding agent according to claim 2, is characterised in that described binding agent is PVP K30.
4. PVP K30 according to claim 3, the consumption of PVP K30 is the percentage by weight of modified glucose is 0.1% ~ 0.1%, is preferably 0.1% ~ 0.5%, is more preferably 0.1% ~ 0.3%.
5. modified glucose described in claim 2, adopts water and ethanol as the solvent of PVP K30 by binding agent, and Dextrose Monohydrate is granulated, to be dried and after granulate, modified glucose water content is 0.5% ~ 3%.
6. claim 1, the clotrimazole buccal tablet described in 2, it be clotrimazole is 10mg that every single dosage contains active component.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109316456A (en) * | 2018-11-21 | 2019-02-12 | 南京泽恒医药技术开发有限公司 | A kind of clotrimazole lozenge and preparation method thereof |
| CN112618502A (en) * | 2020-12-31 | 2021-04-09 | 浙江圣博康药业有限公司 | High-dissolution clotrimazole vaginal tablet and preparation process thereof |
Citations (3)
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| WO1998011878A1 (en) * | 1996-09-19 | 1998-03-26 | Xyrofin Oy | Directly compressible lactitol and method |
| CN101053565A (en) * | 2006-04-12 | 2007-10-17 | 北京德众万全药物技术开发有限公司 | Vaginal tablets containing coltrimazole |
| CN103830198A (en) * | 2012-11-28 | 2014-06-04 | 南京亿华药业有限公司 | Clotrimazole vaginal tablet and preparation method thereof |
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2015
- 2015-07-10 CN CN201510401211.0A patent/CN105030707B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998011878A1 (en) * | 1996-09-19 | 1998-03-26 | Xyrofin Oy | Directly compressible lactitol and method |
| CN101053565A (en) * | 2006-04-12 | 2007-10-17 | 北京德众万全药物技术开发有限公司 | Vaginal tablets containing coltrimazole |
| CN103830198A (en) * | 2012-11-28 | 2014-06-04 | 南京亿华药业有限公司 | Clotrimazole vaginal tablet and preparation method thereof |
Non-Patent Citations (3)
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| BAYER CORPORATION: "MYCELEX®(clotrimazole) TROCHE", 《HTTPS://WWW.ACCESSDATA.FDA.GOV/DRUGSATFDA_DOCS/LABEL/2002/18713SLR019_MYCELEX_LBL.PDF》 * |
| MADGULKAR: "Sugars as solid dispersion carrier to improve solubility and dissolution of the BCS class II drug: clotrimazole", 《DRUG DEV IND PHARM》 * |
| TONGLAIROUM ET AL.: "Fast-Acting Clotrimazole Composited PVP/HPβCD Nanofibers for Oral Candidiasis Application", 《PHARM RES》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109316456A (en) * | 2018-11-21 | 2019-02-12 | 南京泽恒医药技术开发有限公司 | A kind of clotrimazole lozenge and preparation method thereof |
| CN112618502A (en) * | 2020-12-31 | 2021-04-09 | 浙江圣博康药业有限公司 | High-dissolution clotrimazole vaginal tablet and preparation process thereof |
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