CN104490828A - Dexamethasone composition freeze-dried tablet and preparation method thereof - Google Patents

Abstract

The invention provides a dexamethasone composition freeze-dried tablet and a preparation method thereof, and relates to the technical fields of medicines and medicine production. The dexamethasone composition freeze-dried tablet comprises dexamethasone, starch and sucrose; the starch and the sucrose are taken as auxiliary materials; and heating process treatment is carried out on ordinary corn starch, so that the bonding and disintegrating effects of the starch in the tablet can be improved; and the moldability of the tablet is improved. The dexamethasone composition freeze-dried tablet only requires two auxiliary materials namely the starch and the sucrose, and adopts a two-fall and two-lift freeze-drying process, so that the moldability of the tablet can be improved by cooling twice and heating twice; and the dissolution rate of the tablet is improved, thus the bioavailability of the tablet is improved; the defects of an ordinary dexamethasone tablet are overcome; the variety and the amount of auxiliary materials in the dexamethasone tablet are reduced; the tablet is high in dissolution rate, and high in bioavailability; and the curative effect and the safety of clinical medication are ensured.

Description

A kind of dexamethasone compositions lyophilizing 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 dexamethasone compositions lyophilizing sheet and preparation method thereof.

Background technology

Dexamethasone tablet, indication is Aeroseb-Dex.Mainly be applicable to anaphylaxis and auto-immune inflammatory disease, as connective tissue disease, serious bronchial asthma, the anaphylactic diseases such as dermatitis, ulcerative colitis, acute leukemia, malignant lymphoma etc.This medicine is also for the diagnosis of some adrenal cortex disease---dexamethasone suppression test.

Structural formula:

Molecular weight: 392.47

In common dexamethasone 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 dexamethasone tablet quality standard, the dissolution of dexamethasone tablet 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 dexamethasone tablet, improve dissolution and the bioavailability of dexamethasone 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 dexamethasone 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 dexamethasone compositions 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 dexamethasone compositions lyophilizing sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common dexamethasone tablet, decrease supplementary product kind and consumption in dexamethasone tablet, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of dexamethasone compositions lyophilizing sheet, is prepared from by following raw material:

A preparation method for dexamethasone compositions 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 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 dexamethasone 0.75 gram, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring dexamethasone 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 dexamethasone compositions 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 dexamethasone compositions 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 dexamethasone compositions lyophilizing sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Dexamethasone compositions lyophilizing sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in dexamethasone compositions 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 furosemide 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 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 dexamethasone 0.75g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring dexamethasone 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 dexamethasone compositions 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 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 dexamethasone 0.75 gram (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring dexamethasone 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 dexamethasone compositions lyophilizing sheet.

Experimental data

The dexamethasone compositions lyophilizing sheet that above-described embodiment is obtained carries out following quality research test:

1, hardness, friability contrast test

Get dexamethasone compositions lyophilizing sheet prepared by above-described embodiment respectively and dexamethasone 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	61	<1％
Execute example 2	68	<1％
			Ordinary tablet	73	<1％

Experimental data shows, dexamethasone compositions 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 dexamethasone tablet (commercially available) and each 6 of dexamethasone compositions 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 hydrochloric acid solution (9 → 1000) 1000mL for dissolution medium, rotating speed is 75 turns per minute, operate in accordance with the law, respectively through 15min, 25min, 35min, 45min, during 75min, get solution to filter, get subsequent filtrate, according to Chinese Pharmacopoeia (2010 editions) second annex VD high performance liquid chromatography, be filler with octadecylsilane chemically bonded silica, with acetonitrile-water (28 ︰ 72) for mobile phase, determined wavelength is 240nm, get solution 20ul injection liquid chromatography, record chromatogram, another precision takes dexamethasone reference substance and is about 10mg, puts in 100mL measuring bottle, and add methanol 5, jolting makes dissolving, makes the solution about containing 0.75ug in every 1ml, solution in contrast with dissolution medium dilution.Be measured in the same method, by external standard method with calculated by peak area, obtain final product.Calculate the stripping quantity of every sheet, result is as follows:

One, dexamethasone tablet (commercially available)

Two, dexamethasone 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 dexamethasone tablet quality standard, the dissolution of dexamethasone tablet (commercially available) reached more than 75% for qualified 45 minutes time, actual measurement is 76.4%, and dexamethasone lyophilizing sheet dissolution 25 minutes time reaches 78.2%.It can thus be appreciated that the time that dexamethasone lyophilizing sheet dissolution reaches 75% decreased for about 44.4% (20 minutes) time than dexamethasone tablet (commercially available).So the dexamethasone lyophilizing sheet blood drug level peaking time is shorter than dexamethasone 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 dexamethasone compositions lyophilizing sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for dexamethasone compositions 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 dexamethasone 0.75 gram, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring dexamethasone 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 dexamethasone compositions lyophilizing sheet.