CN104546674A - Sulpiride composition freeze-drying tablet and preparation method thereof - Google Patents

Abstract

The invention provides a sulpiride composition freeze-drying tablet and a preparation method thereof, and relates to the technical field of medicine manufacture. The sulpiride composition freeze-drying tablet comprises sulpiride, starch and saccharose; the starch and the saccharose are used as auxiliary materials; common corn starch is treated by a heating process, the adhesion and disintegrating effects of the starch in the tablet can be improved, the formability of the tablet is improved, and the sulpiride composition freeze-drying tablet only needs the two auxiliary materials including the starch and the saccharose. The sulpiride composition freeze-drying tablet adopts a twice-cooling and twice-heating freeze-drying process, through twice-cooling and twice heating, the formability of the tablet can be better, and the dissolution rate of the tablet is improved, so that the bioavailability of the tablet is improved. The tablet overcomes the defects of common sulpiride tablets, the kinds and the use amount of the auxiliary materials in the sulpiride composition freeze-drying tablet are reduced, the dissolution rate of the tablet is high, the bioavailability is high, and the treatment effect and the safety of clinical medication are ensured.

Description

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

Background technology

Sulpiride tablet to indifferent, shrink back, the effect of numb, depressed, hallucination and vain hope symptom is better, be applicable to schizophrenia simple type, intolerance style, catatonic type and chronic schizophrenia unsociable and eccentric, shrink back, indifferent symptom.

Molecular weight: 341.42

In common Sulpiride 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 Sulpiride tablet quality standard, the dissolution of Sulpiride tablet reached more than 75% for qualified 20 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 Sulpiride tablet, improve dissolution and the bioavailability of Sulpiride 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 sulpiride 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 sulpiride 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 sulpiride composition freeze-drying sheet, does adjuvant with starch and sucrose, produces with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common Sulpiride tablet, decreases supplementary product kind and consumption in Sulpiride tablet, and this sheet dissolution is large, bioavailability is high, ensure that curative effect and the safety of clinical application.

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

A preparation method for sulpiride 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, 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 sulpiride 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

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

Beneficial effect of the present invention is:

The preparation method of a kind of sulpiride 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 sulpiride composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Sulpiride composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in sulpiride 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 sulpiride 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, 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 sulpiride 10g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

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

Embodiment 2

A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5-7, 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 sulpiride 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 sulpiride 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 sulpiride composition freeze-drying sheet.

Experimental data

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

1, hardness, friability contrast test

Get sulpiride composition freeze-drying sheet prepared by above-described embodiment respectively and sulpiride 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	<1％
Execute example 2	66	<1％
			Ordinary tablet	68	<1％

Experimental data shows, sulpiride 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 Sulpiride tablet (commercially available) and each 6 of sulpiride composition freeze-drying sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex X C the 3rd method respectively, with 0.lmol/L hydrochloric acid solution 200ml (10mg specification) for dissolution medium, rotating speed is 35 turns (lOmg specifications), operates, through 5 minutes in accordance with the law, 10 minutes

20 minutes, 30 minutes, when 50 minutes, get solution appropriate, filter, get subsequent filtrate appropriate, make the solution about containing sulpiride 50mg in every lml with the dilution of 0.lmol/L hydrochloric acid solution, according to ultraviolet visible spectrophotometry (annex IV A), measure absorbance at the wavelength place of 291nm; Separately get sulpiride reference substance, accurately weighed, add 0.lmol/L dissolve with hydrochloric acid solution and quantitatively dilute the solution made about containing 50 μ g in every lml, being measured in the same method, calculating the stripping quantity of every sheet.

One, Sulpiride tablet (commercially available)

Two, sulpiride 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 Sulpiride tablet quality standard, the dissolution of sulpiride degree sheet (commercially available) reached more than 75% for qualified 20 minutes time, actual measurement is 77.4%, and the stripping 10 minutes time of sulpiride lyophilizing sheet reaches 77.2%.It can thus be appreciated that the time that sulpiride lyophilizing sheet dissolution reaches 75% decreased for about 50% (10 minutes) time than Sulpiride tablet (commercially available).So the sulpiride lyophilizing sheet blood drug level peaking time is shorter than Sulpiride 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 sulpiride composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for sulpiride 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, 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 sulpiride 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

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