CN104490751A - Hydrochlorothiazide composition freeze-dried tablets and preparation method thereof - Google Patents
Hydrochlorothiazide composition freeze-dried tablets and preparation method thereof Download PDFInfo
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- CN104490751A CN104490751A CN201410736120.8A CN201410736120A CN104490751A CN 104490751 A CN104490751 A CN 104490751A CN 201410736120 A CN201410736120 A CN 201410736120A CN 104490751 A CN104490751 A CN 104490751A
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Abstract
The invention provides hydrochlorothiazide composition freeze-dried tablets and a preparation method thereof and relates to the technical field of medicines and medical production. The tablets comprise hydrochlorothiazide, starch and cane sugar, the starch and cane sugar are taken as auxiliary materials, the common corn starch is treated by a heating technology, the adhesion and disintegration effects of the starch in the tablets can be improved, the formability of the tablets is improved, and only two auxiliary materials, namely the starch and cane sugar are needed by the hydrochlorothiazide composition freeze-dried tablets. According to the hydrochlorothiazide composition freeze-dried tablets, a two-cooling and two-heating freeze-drying process is adopted, the tablet formability can be higher by virtue of cooling twice and heating twice, and the dissolution rate of the tablets is improved, so that the bioavailability of the tablets is improved. According to the tablets, the defects of common hydrochlorothiazide tablets are overcome, the types and amount of the auxiliary materials in the hydrochlorothiazide tablets are reduced, the tablets are high in dissolution rate and high in bioavailability, and the curative effect and safety of clinical medication are guaranteed.
Description
Technical field
The present invention relates to medicine and medical production technical field, be specifically related to a kind of hydrochlorothiazide composition lyophilizing sheet and preparation method thereof.
Background technology
Hydrochlorothiazide is benzo thiazides diuretic.There is gentleness and lasting hypotensive effect.It is to Patients with Senile Hypertension, and long-term low dose of medication can control blood pressure preferably, and can reduce the heart, brain, the sickness rate of vascular complication and case fatality rate.
Structural formula:
molecular weight: 297.74
In common hydrochlorothiazide tablet containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second hydrochlorothiazide tablet quality standard, the dissolution of hydrochlorothiazide tablet reached more than 75% for qualified 60 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 hydrochlorothiazide tablet, improve dissolution and the bioavailability of hydrochlorothiazide tablet, 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 hydrochlorothiazide 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 hydrochlorothiazide composition lyophilizing 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 hydrochlorothiazide composition lyophilizing sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common hydrochlorothiazide tablet, decrease supplementary product kind and consumption in hydrochlorothiazide tablet, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.
A kind of hydrochlorothiazide composition lyophilizing sheet, is prepared from by following raw material:
A preparation method for hydrochlorothiazide composition lyophilizing 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 5-7.5, 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 100m L, 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 hydrochlorothiazide 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring hydrochlorothiazide 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 hydrochlorothiazide composition lyophilizing 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 hydrochlorothiazide composition lyophilizing 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 hydrochlorothiazide composition lyophilizing sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Hydrochlorothiazide composition lyophilizing sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in hydrochlorothiazide composition lyophilizing 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 hydrochlorothiazide 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 5-7.5, 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 100m L, 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 hydrochlorothiazide 10g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring hydrochlorothiazide 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 hydrochlorothiazide composition lyophilizing sheet.
Embodiment 2
A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5-7.5, 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 100m L, 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 hydrochlorothiazide 10 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring hydrochlorothiazide 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 hydrochlorothiazide composition lyophilizing sheet.
Experimental data
The hydrochlorothiazide composition lyophilizing sheet that above-described embodiment is obtained carries out following quality research test:
1, hardness, friability contrast test
Get hydrochlorothiazide composition lyophilizing sheet prepared by above-described embodiment respectively and hydrochlorothiazide 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 |
Execute example 1 | 66.2 | <1% |
Execute example 2 | 64.9 | <1% |
Ordinary tablet | 66.5 | <1% |
Experimental data shows, hydrochlorothiazide composition lyophilizing 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 hydrochlorothiazide tablet (commercially available) and each 6 of hydrochlorothiazide composition lyophilizing sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex X C first method respectively, with 0.1mol/L hydrochloric acid solution for dissolution medium, rotating speed is 100 turns per minute, operate in accordance with the law, respectively through 10min, 20min, 40min, 60min, during 90min, get solution 10ml to filter, it is appropriate that precision measures continuous worry liquid, the solution containing 5 ~ 10ug in every 1ml is made with dissolution medium dilution, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 237nm, another precision takes hydrochlorothiazide reference substance, accurately weighed, dissolves and is quantitatively diluted to the solution about containing 5 ~ 10ug in every 1ml, be measured in the same method, calculate the stripping quantity of every sheet with dissolution medium.Result is as follows:
One, hydrochlorothiazide tablet (commercially available)
Two, hydrochlorothiazide 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 hydrochlorothiazide tablet quality standard, the dissolution of hydrochlorothiazide tablet (commercially available) reached more than 75% for qualified 60 minutes time, actual measurement is 79.4%, and hydrochlorothiazide lyophilizing sheet dissolution 20 minutes time reaches 79.4%.It can thus be appreciated that the time that hydrochlorothiazide lyophilizing sheet dissolution reaches 75% is than the time decreasing about 40 minutes of hydrochlorothiazide tablet (commercially available).So the hydrochlorothiazide lyophilizing sheet blood drug level peaking time is shorter than hydrochlorothiazide tablet (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 hydrochlorothiazide composition lyophilizing sheet, is characterized in that, is prepared from by following raw material:
2. a preparation method for hydrochlorothiazide composition lyophilizing 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 5-7.5, 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 hydrochlorothiazide 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring hydrochlorothiazide 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 hydrochlorothiazide composition lyophilizing sheet.
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Cited By (1)
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CN107519140A (en) * | 2016-06-21 | 2017-12-29 | 北京科信必成医药科技发展有限公司 | A kind of Hydrochioro microplate and preparation method thereof |
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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 |
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Patent Citations (2)
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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 |
Non-Patent Citations (2)
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刘晓睿 等: "《口腔速溶片的研究进展》", 《中南药学》 * |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN107519140A (en) * | 2016-06-21 | 2017-12-29 | 北京科信必成医药科技发展有限公司 | A kind of Hydrochioro microplate and preparation method thereof |
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Application publication date: 20150408 |