CN104546859A - Dimenhydrinate composition freeze-dried tablets and preparation method thereof - Google Patents

Abstract

The invention provides dimenhydrinate composition freeze-dried tablets and a preparation method thereof, and relates to the technical field of medicine and medicine production. The dimenhydrinate composition freeze-dried tablets comprise dimenhydrinate, starch and sucrose, wherein starch and sucrose are used as accessories. Ordinary corn starch is treated by a heating process, so that the bonding and disintegration effects of starch in the tablets can be improved, and the forming property of the tablets can be improved; only starch and sucrose are required to be used as the accessories of the dimenhydrinate composition freeze-dried tablets. A two-cooling two-heating freeze-drying process is adopted for the dimenhydrinate composition freeze-dried tablets, and by twice cooling and twice heating, better forming property of the tablets can be achieved, and the dissolubility of the tablets is improved, so that the bioavailability of the tablets is improved. According to the tablets, the defects of ordinary dimenhydrinate tablets are overcome, the sort and using amounts of the accessories in the dimenhydrinate tablets are reduced, the tablets are high in dissolubility and bioavailability, and the curative effects and safety of clinical mediation are ensured.

Description

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

Background technology

Dimenhydrinate dimenhydrinate is a kind of antihistaminic Western medicine, and mainly with its anti-motion sickness, to gestation, Meniere, the Nausea and vomiting that radiation cure etc. cause, dizzyly also has certain effect.

Molecular weight: 469.97

In common dimenhydrinate 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 dimenhydrinate tablets quality standard, the dissolution of dimenhydrinate 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 dimenhydrinate tablets, improve dissolution and the bioavailability of dimenhydrinate 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 dimenhydrinate 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 dimenhydrinate 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 dimenhydrinate 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 dimenhydrinate tablets, decrease supplementary product kind and consumption in dimenhydrinate tablets, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

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

A preparation method for dimenhydrinate 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 5.5-7.0, 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 dimenhydrinate 25 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring dimenhydrinate 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 dimenhydrinate 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 dimenhydrinate 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 dimenhydrinate composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Dimenhydrinate composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in dimenhydrinate 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 dimenhydrinate 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 is controlled then to be heated to 72 DEG C at 5.5-7.0 by the pH value of solution, keep 120 minutes, make the corn starch solution of 9% (W/V) by pH adjusting agent.

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 dimenhydrinate 25g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

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

Embodiment 2

A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5.5-7.0, 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 dimenhydrinate 25 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

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

Experimental data

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

1, hardness, friability contrast test

Get dimenhydrinate composition freeze-drying sheet prepared by above-described embodiment respectively and dimenhydrinate ordinary tablet (commercially available) detects friability and hardness by " Chinese Pharmacopoeia " version in 2010 two annex XG 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	64	<1％
			Ordinary tablet	67	<1％

Experimental data shows, dimenhydrinate 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 dimenhydrinate tablets (commercially available) and each 6 of dimenhydrinate composition freeze-drying sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex XC second method respectively, with water 900mL for dissolution medium, rotating speed is 50 turns per minute, operate in accordance with the law, respectively through 15min, 25min, 35min, 45min, during 75min, get solution 10ml, filter, precision measures subsequent filtrate 5ml and puts in 20ml measuring bottle (50mg specification) or 10ml measuring bottle (25mg specification), be diluted with water to scale, shake up, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, separately get dimenhydrinate reference substance, accurately weighed, be dissolved in water and quantitatively dilute the solution made about containing 14ug in every 1ml, being measured in the same method, calculating the stripping quantity of every sheet.Result is as follows:

One, dimenhydrinate tablets (commercially available)

Two, dimenhydrinate 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 dimenhydrinate tablets quality standard, the dissolution of dimenhydrinate tablets (commercially available) reached more than 75% for qualified 45 minutes time, actual measurement is 76.2%, and dimenhydrinate lyophilizing sheet dissolution 25 minutes time reaches 77.2%.It can thus be appreciated that the time that dimenhydrinate lyophilizing sheet dissolution reaches 75% decreased for about 66.7% (20 minutes) time than dimenhydrinate tablets (commercially available).So the dimenhydrinate lyophilizing sheet blood drug level peaking time is shorter than dimenhydrinate 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 dimenhydrinate composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for dimenhydrinate 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 5.5-7.0, 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 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 dimenhydrinate 25 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

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