CN104473863A - Benzbromarone composition lyophilized tablet and preparation method thereof - Google Patents
Benzbromarone composition lyophilized tablet and preparation method thereof Download PDFInfo
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- CN104473863A CN104473863A CN201410736905.5A CN201410736905A CN104473863A CN 104473863 A CN104473863 A CN 104473863A CN 201410736905 A CN201410736905 A CN 201410736905A CN 104473863 A CN104473863 A CN 104473863A
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Abstract
The invention provides a benzbromarone composition lyophilized tablet and a preparation method thereof, and relates to the technical field of medicines and medicine production. The tablet is prepared from benzbromarone, starch and cane sugar, wherein starch and cane sugar are used as auxiliaries, common corn starch is subjected to heating treatment to improve the adhering and disintegrating effects of the starch in the tablet, so that the moldability of the tablet can be improved. The benzbromarone composition lyophilized tablet only needs starch and cane sugar two auxiliaries. According to the preparation method, a twice-cooling twice-heating lyophilizing process is adopted for the benzbromarone composition lyophilized tablet, the moldability of the tablet can be better by means of twice cooling and twice heating, the solubility of the tablet can be improved, and the bioavailability of the tablet can be improved; the tablet is capable of overcoming the defect of conventional benzbromarone tablets and reducing the types and usage of auxiliaries in the benzbromarone tablets, is high in solubility and high in bioavailability, and can be used for guaranteeing the curative effect and safety of clinical administration.
Description
Technical field
The present invention relates to medicine and medical production technical field, be specifically related to a kind of benzbromarone composition freeze-drying sheet and preparation method thereof.
Background technology
Benzbromarone belongs to benzofuran derivative, is uricosureic agent, and mechanism of action is mainly fixed by suppressing renal tubules to the heavily absorption of uric acid, thus reduces uric acid concentration in blood.Primary hyperuricemia, gouty joint moxibustion intermission and tophus swell
chemical structural formula
Molecular weight: 424.09
In common benzbromarone tablets containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second benzbromarone tablets quality standard, the dissolution of benzbromarone tablets reached more than 75% for qualified 45 minutes time, and increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine.
Therefore, provide one can overcome above-mentioned shortcoming, select suitable adjuvant and technique, reduce supplementary product kind and consumption in benzbromarone tablets, improve dissolution and the bioavailability of benzbromarone tablets, ensure that the safety of clinical application all has positive effect.
Traditional lyophilizing tablet can improve dissolution and bioavailability, but still need use the adjuvant such as mannitol, gelatin.And mannitol has certain biological activity, gelatin resource-constrained and perishable.
Starch is the basic adjuvant of oral solid formulation, it is polymerized by glucose molecule, and be commonly used for adhesive, diluent and disintegrating agent in tablets, it is cheap and easy to get, to human-body safety, but being used alone starch has no report as adjuvant freeze-dry process production benzbromarone lyophilizing sheet.
Summary of the invention
Technical problem to be solved by this invention is the defect overcoming prior art, and propose a kind of benzbromarone composition freeze-drying sheet and preparation method thereof further, said preparation adjuvant is few, good stability, and bioavailability is high.
Technical problem to be solved by this invention realizes by the following technical solutions:
A kind of benzbromarone composition freeze-drying sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common benzbromarone tablets, decrease supplementary product kind and consumption in benzbromarone tablets, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.
A kind of benzbromarone composition freeze-drying sheet, is prepared from by following raw material:
A preparation method for benzbromarone composition freeze-drying sheet, comprises step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 5-7.0, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100ml, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take benzbromarone 50 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring benzbromarone content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain benzbromarone composition freeze-drying sheet.
Described starch selects corn starch, preferably the corn starch solution of 10% (W/V).
Beneficial effect of the present invention is:
The preparation method of a kind of benzbromarone composition freeze-drying sheet of the present invention, heating process process is carried out to common corn starch, starch bonding in tablets, disintegration can be improved, improve the mouldability of tablet, in benzbromarone composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Benzbromarone composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in benzbromarone composition freeze-drying sheet employing two, and twice cooling, twice intensification can make sheet mouldability better, which increase the dissolution of tablet, thus improve the bioavailability of tablet.
Accompanying drawing explanation
Fig. 1 is the dissolution correlation curve figure of benzbromarone in experiment.
Detailed description of the invention
The technological means realized to make the present invention, creation characteristic, reaching object and effect is easy to understand, below in conjunction with specific embodiment, set forth the present invention further, but following embodiment being only the preferred embodiments of the present invention, and not all.Based on the embodiment in embodiment, those skilled in the art under the prerequisite not making creative work obtain other embodiment, all belong to the protection domain of this patent.
Embodiment 1
A, take the corn starch of 100g, the purified water adding 900ml stirs, and controls at 5-7.0, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 9% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take benzbromarone 50g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring benzbromarone content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain benzbromarone composition freeze-drying sheet.
Embodiment 2
A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5-7.0, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 13% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take benzbromarone 50 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring benzbromarone content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain benzbromarone composition freeze-drying sheet.
Experimental data
The benzbromarone composition freeze-drying sheet that above-described embodiment is obtained carries out following quality research test:
1, hardness, friability contrast test
Get benzbromarone composition freeze-drying sheet prepared by above-described embodiment respectively and benzbromarone ordinary tablet (commercially available) detects friability and hardness by " Chinese Pharmacopoeia " version in 2010 two annex X G inspection techniques, carried out comparative study, the results are shown in following table:
Sample | Hardness/N | Friability |
Embodiment 1 | 66.5 | <1% |
Embodiment 2 | 64 | <1% |
Ordinary tablet (commercially available) | 69 | <1% |
Experimental data shows, benzbromarone composition freeze-drying sheet and ordinary tablet (commercially available) without significant difference, meet " Chinese Pharmacopoeia " version in 2010 to the requirement of tablet on friability and hardness.
2, dissolution contrast test
(No. 1 to No. 3 is embodiment 1 to get benzbromarone tablets (commercially available) and each 6 of benzbromarone composition freeze-drying sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex X C second method respectively, (sodium hydrogen phosphate 12.5g is got with phosphate buffer, potassium dihydrogen phosphate 1.46g and sodium lauryl sulphate 2.5g, be dissolved in water and be diluted to 1000ml, pH value to 7.5 is regulated with 2mol/L sodium hydroxide solution) 1000ml is dissolution medium, rotating speed is 100 turns per minute, operate in accordance with the law, respectively through 10min, 20min, 30min, 45min, during 75min, get solution appropriate, filter, precision measures subsequent filtrate 5ml, put in 25ml measuring bottle, scale is diluted to dissolution medium, shake up, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 356nm, separately take benzbromarone reference substance, accurately weighed, add stripping medium dissolves and quantitatively dilute the solution made about containing 10ug in every 1ml, being measured in the same method, calculating the stripping quantity of every sheet.Result is as follows:
One, benzbromarone tablets (commercially available)
Two, benzbromarone lyophilizing sheet (No. 1 to No. 3 is embodiment 1, and No. 4 to No. 6 is embodiment 2)
Respectively with catch cropping Dissolution profiles during average dissolution pair, as Fig. 1.
Four, result judges
Judge according to Chinese Pharmacopoeia (2010 editions) second benzbromarone tablets quality standard, the dissolution of benzbromarone tablets (commercially available) reached more than 75% for qualified 45 minutes time, actual measurement is 75.4%, and benzbromarone lyophilizing sheet dissolution 20 minutes time reaches 77.4%.It can thus be appreciated that the time that benzbromarone lyophilizing sheet dissolution reaches 75% decreased for about 55.6% (25 minutes) time than benzbromarone tablets (commercially available).So the benzbromarone lyophilizing sheet blood drug level peaking time is shorter than benzbromarone tablets (commercially available), and bioavailability is higher, better efficacy.
More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (2)
1. a benzbromarone composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:
2. a preparation method for benzbromarone composition freeze-drying sheet according to claim 1, is characterized in that, comprise step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 5-7.0, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100ml, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take benzbromarone 50 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring benzbromarone content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain benzbromarone composition freeze-drying sheet.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
CN102429881A (en) * | 2011-12-01 | 2012-05-02 | 常州康普药业有限公司 | Method for preparing benzbromarone tablets |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
CN102429881A (en) * | 2011-12-01 | 2012-05-02 | 常州康普药业有限公司 | Method for preparing benzbromarone tablets |
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Application publication date: 20150401 |