CN104434833A - Melbine composition freeze-dried tablet and preparation method thereof - Google Patents

Abstract

The invention provides a melbine composition freeze-dried tablet and a preparation method thereof, and relates to the technical field of medicine production. The melbine composition freeze-dried tablet consists of melbine, starch and sucrose, wherein the starch and the sucrose are used as accessories; the normal corn starch is subjected to heating process treatment, so that the bonding and disintegration effects of the starch in the tablet are enhanced, and the formability of the tablet is improved; only two accessories, namely the starch and the sucrose, are required by the melbine composition freeze-dried tablet. By virtue of a twice-heating and twice-cooling freeze-drying process, the melbine composition freeze-dried tablet has better formability due to the process of cooling twice and heating twice, and the dissolution rate of the tablet is improved, so that the bioavailability of the tablet is improved; the tablet is capable of overcoming the shortcomings of a normal melbine tablet and reducing the variety and dosage of accessories in the melbine tablet; and the tablet is high in dissolution rate and bioavailability, so that the curative effect and safety of clinical medication are guaranteed.

Description

A kind of combination with metformin thing 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 combination with metformin thing lyophilizing sheet and preparation method thereof.

Background technology

Metformin is biguanides oral hypoglycemic.There is multiple mechanism of action, comprise delay glucose and absorbed by gastrointestinal, increasing the utilization of periphery glucose by improving the sensitivity of insulin, and the gluconeogenesis suppressing liver, kidney excessive, do not reduce the blood sugar level of ND.

Structural formula:

Molecular weight: 165.63

In common diformin 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 diformin tablet quality standard, reach more than 70% for qualified during the dissolution 45 minutes of diformin tablet, 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 diformin tablet, improve dissolution and the bioavailability of diformin 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 metformin 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 combination with metformin thing 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 combination with metformin thing lyophilizing sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common diformin tablet, decrease supplementary product kind and consumption in diformin tablet, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of combination with metformin thing lyophilizing sheet, is prepared from by following raw material:

A preparation method for combination with metformin thing 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 metformin 250 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring metformin 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 combination with metformin thing 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 combination with metformin thing 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 combination with metformin thing lyophilizing sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Combination with metformin thing lyophilizing sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in combination with metformin thing 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 900m l 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 metformin 250g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring metformin 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 combination with metformin thing 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 metformin 250 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring metformin 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 combination with metformin thing lyophilizing sheet.

Experimental data

The combination with metformin thing lyophilizing sheet that above-described embodiment is obtained carries out following quality research test:

The combination with metformin thing lyophilizing sheet that present embodiment is obtained carries out following quality research test:

1, hardness, friability contrast test

Get combination with metformin thing lyophilizing sheet prepared by above-described embodiment respectively and metformin 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	63	<1％
Execute example 2	65	<1％
			Ordinary tablet	69	<1％

Experimental data shows, combination with metformin thing 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 diformin tablet (commercially available) and each 6 of combination with metformin thing 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 water 1000mL for dissolution medium, rotating speed is 100 turns per minute, operate in accordance with the law, respectively through 15min, 25min, 35min, 45min, during 75min, get solution appropriate, filter, discard just filtrate 10ml, it is appropriate that precision measures subsequent filtrate, 50 times are 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 233nm, separately get metformin reference substance, accurately weighed, be dissolved in water and quantitatively dilute the solution made about containing 5ug in every 1ml, being measured in the same method, calculating the stripping quantity of every sheet.Result is as follows:

One, diformin tablet (commercially available)

Two, metformin 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 diformin tablet quality standard, the dissolution of diformin tablet (commercially available) reached more than 70% for qualified 45 minutes time, actual measurement is 73.1%, and metformin lyophilizing sheet dissolution 25 minutes time reaches 75.4%.It can thus be appreciated that the time that metformin lyophilizing sheet dissolution reaches 70% decreased for about 44.4% (20 minutes) time than diformin tablet (commercially available).So the metformin lyophilizing sheet blood drug level peaking time is shorter than diformin 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 combination with metformin thing lyophilizing sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for combination with metformin thing 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 metformin 250 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring metformin 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 combination with metformin thing lyophilizing sheet.