CN104546756A - Amoxicillin composition freeze-dried tablet and preparation method thereof - Google Patents

Abstract

The invention provides an amoxicillin composition freeze-dried tablet and a preparation method thereof, and relates to the technical field of medicines and medicine production. The amoxicillin composition freeze-dried tablet comprises amoxicillin, starch and cane sugar, wherein the starch and the cane sugar are taken as auxiliary materials. Common corn starch is treated by a heating process, so that the bonding and disintegration functions of the starch in the tablet can be improved, and the formability of the tablet is improved. The amoxicillin composition freeze-dried tablet only needs two auxiliary materials namely the starch and the cane sugar. The amoxicillin composition freeze-dried tablet adopts the freeze-drying process that temperature is reduced and increased for two times respectively, and the process that temperature is reduced and increased for two times enables the formability of the tablet to be better and increases the dissolution rate of the tablet so as to improve the biological availability of the tablet; the tablet overcomes the defects of a common amoxicillin tablet, the types and dosage of auxiliary materials in the amoxicillin tablet are reduced, the dissolution rate of the tablet is high, the biological availability of the tablet is high, and the curative effect and the safety of clinical medication are ensured.

Description

A kind of amoxicillin composition freeze-drying sheet and preparation method thereof

Technical field

The present invention relates to medicine and medical production technical field, be specifically related to a kind of amoxicillin composition freeze-drying sheet and preparation method thereof.

Background technology

Amoxicillin is a kind of the most frequently used penicillins wide spectrum beta-lactam antibiotic.Stablize in acid condition, gastrointestinal absorption rate reaches 90.Amoxicillin bactericidal action is strong, and the ability of penetration cell wall is also strong.Be one of current widely used oral penicillin, its preparation has capsule, tablet, granule, dispersible tablet etc.Penicillin anaphylaxis and penicillin skin test positive patient forbidding.

Chemical formula: C ₁₆h ₁₉n ₃o ₅s3H ₂o

Molecular weight: 419.46

In common amoxicillin 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 amoxicillin tablets quality standard, the dissolution of amoxicillin tablets reached more than 80% for qualified 30 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 amoxicillin tablets, improve dissolution and the bioavailability of amoxicillin 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 amoxicillin 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 amoxicillin 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 amoxicillin 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 amoxicillin tablets, decrease supplementary product kind and consumption in amoxicillin tablets, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of amoxicillin composition freeze-drying sheet, is prepared from by following raw material:

A preparation method for amoxicillin 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 5.2-7.5, 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 125 grams, amoxicillin, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of amoxicillin 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 amoxicillin 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 amoxicillin of the present invention composition freeze-drying sheet, heating process process is carried out to common corn starch, starch bonding in tablets, disintegration can be improved, improve the mouldability of tablet, in the composition freeze-drying sheet of amoxicillin, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Amoxicillin composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in amoxicillin 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 amoxicillin 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 900m l stirs, and controls at 5.2-7.5, 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 125 grams, amoxicillin, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of amoxicillin 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 amoxicillin composition freeze-drying sheet.

Embodiment 2

A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5.2-7.5, 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 125 grams, amoxicillin (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of amoxicillin 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 amoxicillin composition freeze-drying sheet.

Experimental data

The amoxicillin composition freeze-drying sheet that above-described embodiment is obtained carries out following quality research test:

1, hardness, friability contrast test

Get amoxicillin composition freeze-drying sheet prepared by above-described embodiment respectively and amoxicillin 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	65	<1％
Execute example 2	64	<1％
			Ordinary tablet	66	<1％

Experimental data shows, amoxicillin 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 amoxicillin tablets (commercially available) and each 6 of amoxicillin 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, with water 900mL for dissolution medium, rotating speed is 75 turns per minute, operate in accordance with the law, respectively through 10mi n, 15mi n, 20mi n, 30mi n, during 60mi n, get solution appropriate, filter, it is appropriate that precision measures subsequent filtrate, the solution made about containing 130 μ g in every 1ml is quantitatively diluted with water, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 272nm, separately get this product 10, porphyrize, precision takes in right amount (being about equivalent to average sheet weight), is dissolved in water and also quantitatively dilutes the solution made about containing 130 μ g in every 1mL, filter, get subsequent filtrate, be measured in the same method, calculate the stripping quantity of every sheet by labelled amount.Result is as follows:

One, amoxicillin tablets (commercially available)

Two, amoxicillin 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 amoxicillin tablets quality standard, the dissolution of amoxicillin tablets (commercially available) reached more than 80% for qualified 30 minutes time, actual measurement is 81.4%, and amoxicillin lyophilizing sheet dissolution 15 minutes time reaches 82.4%.It can thus be appreciated that the time that amoxicillin lyophilizing sheet dissolution reaches 80% decreased for about 50% (15 minutes) time than amoxicillin tablets (commercially available).So the amoxicillin lyophilizing sheet blood drug level peaking time is shorter than amoxicillin 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. an amoxicillin composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for amoxicillin according to claim 1 composition freeze-drying sheet, 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 5.2-7.5, 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 125 grams, amoxicillin, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of amoxicillin 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 amoxicillin composition freeze-drying sheet.