CN104490827A - Fenofibrate composition freeze-dried tablet and preparation method thereof - Google Patents

Abstract

The invention provides a fenofibrate composition freeze-dried tablet and a preparation method thereof, and relates to the technical fields of medicines and medicine production. The fenofibrate composition freeze-dried tablet comprises fenofibrate, 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 fenofibrate 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 fenofibrate tablet are overcome; the variety and the amount of auxiliary materials in the fenofibrate 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 Fenofibrate composition 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 Fenofibrate composition lyophilizing sheet and preparation method thereof.

Background technology

This product has the concentration significantly reducing serum levels of triglyceride and very low density lipoprotein (VLDL), cholesterol, low density lipoprotein, LDL and apo-B, and high-density lipoprotein, apolipoprotein-A1 and apolipoprotein-A and apo-B E ratio are raised, comparatively the effect of chlorine shellfish fourth fat is strong.

C ₂₀H ₂₁ClO ₄360.84

In common fenofibrate containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second fenofibrate quality standard, the dissolution of fenofibrate reached more than 60% for qualified 60 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 fenofibrate, improve dissolution and the bioavailability of fenofibrate, 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 fenofibrate 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 Fenofibrate composition 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 Fenofibrate composition lyophilizing sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common fenofibrate, decrease supplementary product kind and consumption in fenofibrate, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of Fenofibrate composition lyophilizing sheet, is prepared from by following raw material:

A preparation method for Fenofibrate composition 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 fenofibrate 100 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of Fenofibrate 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 Fenofibrate composition 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 Fenofibrate composition 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 Fenofibrate composition lyophilizing sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Fenofibrate composition lyophilizing sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in Fenofibrate composition 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 fenofibrate 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 fenofibrate 100g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of Fenofibrate 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 Fenofibrate composition 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 fenofibrate 100 grams (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 Fenofibrate 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 Fenofibrate composition lyophilizing sheet.

Experimental data

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

1, hardness, friability contrast test

Get Fenofibrate composition lyophilizing sheet prepared by above-described embodiment respectively and fenofibrate 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	63.5	<1％
Execute example 2	65.8	<1％
			Ordinary tablet (commercially available)	67.3	<1％

Experimental data shows, Fenofibrate composition 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 fenofibrate (commercially available) and each 6 of Fenofibrate composition lyophilizing sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex XC second method respectively, with the phosphate solution 1000mL of 1.0% sodium lauryl sulphate for dissolution medium, rotating speed is 100 turns per minute, operate in accordance with the law, respectively through 10min, 20min, 40min, 60min, during 90min, get solution to filter, get continuous worry liquid, according to Chinese Pharmacopoeia (2010 editions) second annex IVA ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 289nm, another precision takes fenofibrate reference substance and is about 10mg, puts in 100mL measuring bottle, and add acetonitrile and dissolve and be diluted to scale, shake up, precision measures 5mL, puts in 100mL measuring bottle, adds stripping medium to scale, shakes up, be measured in the same method, calculate the stripping quantity of every sheet.Result is as follows:

One, fenofibrate (commercially available)

Two, fenofibrate 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 fenofibrate quality standard, the dissolution of fenofibrate (commercially available) reached more than 60% for qualified 60 minutes time, actual measurement is 78.45%, and fenofibrate lyophilizing sheet dissolution 20 minutes time reaches 76.6%.It can thus be appreciated that the time that fenofibrate lyophilizing sheet dissolution reaches 75% is than the time decreasing about 40 minutes of fenofibrate (commercially available).So the fenofibrate lyophilizing sheet blood drug level peaking time is shorter than fenofibrate (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 Fenofibrate composition lyophilizing sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for Fenofibrate composition 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 fenofibrate 100 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring Determination of Fenofibrate 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 Fenofibrate composition lyophilizing sheet.