CN106265552A

CN106265552A - A kind of preparation method of clarithromycin

Info

Publication number: CN106265552A
Application number: CN201510257378.4A
Authority: CN
Inventors: 陈立春
Original assignee: Chengdu Baoke Biotechnology Co Ltd
Current assignee: Chengdu Baoke Biotechnology Co Ltd
Priority date: 2015-05-19
Filing date: 2015-05-19
Publication date: 2017-01-04

Abstract

The invention provides the preparation method of a kind of clarithromycin, it comprises the steps: a, the raw material weighing each weight proportion and adjuvant: clarithromycin 1-5 part, filler 4.7-8.7 part, disintegrating agent 0.5-1.5 part, lubricant 0.05-0.25 part, binding agent 0.05-0.1 part；B, clarithromycin and disintegrating agent are dissolved in 50-95% ethanol, are prepared as pastille binding agent；C, take filler, lubricant and binder combination and sieve, mixing；D, the pastille binding agent of b step is joined in mixture prepared by step (c), pelletize, be dried, granulate, total mixed, tabletting, be prepared as tablet.Clarithromycin preparation method of the present invention ensure that the medicament contg uniformity, and raw material controls particle diameter without micronization, and this invention can increase the dissolution of insoluble drug, and common dissolving reduces technological operation step, saves the energy, and reduces cost.

Description

A kind of preparation method of clarithromycin

Technical field

The present invention relates to the preparation method of a kind of clarithromycin, belong to field of pharmaceutical preparations.

Background technology

Clarithromycin is a kind of novel macrolide antibiotics similar to erythromycin structure and antimicrobial spectrum, It it is one of the representative of semi-synthetic red enzyme element class new varieties.Can pass through antibacterial cell wall so that with new army ribosome Combination that 5OS subunit can drive in the wrong direction and produce retardance and turn peptide and metathesis, can effectively suppress the prolongation of chain, reduce RNA, according to the synthesis of resistant protein matter, plays bacteriostasis, and its bacteriostatic activity is more than the twice of erythromycin.With Other traditional macrolide antibiotics compares, the pharmacodynamics of clarithromycin and pharmacokinetic profile All having clear improvement, be administered orally in gastrointestinal absorption rapid, absolute bioavailability can reach 55%.Because carat is mould Element is water insoluble, and prepared composition discrete piece can further improve its bioavailability.

Number of patent application CN201310316742.0, denomination of invention: the preparation side of a kind of clarithromycin Method, disclose by clarithromycin and lactose with certain proportion micropowder after, mix with prescription adds adjuvant in other Pelletize with binder aqueous solution again.Though the method improves the dissolution of clarithromycin, but by clarithromycin powder Broken needing special micronization equipment when commercial production, input cost is higher and easily loses raw material, increases work Skill operating process and difficult control.

Summary of the invention

In order to solve above-mentioned technical problem, technical scheme provides a kind of clarithromycin Preparation method.

The invention provides a kind of method preparing clarithromycin, it comprises the steps:

The preparation method of a kind of clarithromycin, it comprises the steps:

A, the raw material weighing each weight proportion and adjuvant:

Clarithromycin 1-5 part, filler 4.7-8.7 part, disintegrating agent 0.5-1.5 part, lubricant 0.05-0.25 Part, binding agent 0.05-0.1 part；

B, clarithromycin and binding agent are dissolved in 50-95% ethanol, are prepared as pastille binding agent；

C, take filler and disintegrant mixture is sieved, mixing；

D, the pastille binding agent of b step is joined in mixture prepared by step (c), pelletize, be dried, Granulate, total mixed, tabletting, be prepared as tablet.

As preferably, described filler is selected from least one in starch, dextrin, lactose, microcrystalline Cellulose.

As preferably, described binding agent is selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl fibre At least one in dimension element sodium.

As preferably, described disintegrating agent is selected from carboxymethylstach sodium, crospolyvinylpyrrolidone, crosslinking carboxylic first At least one in base sodium cellulosate；Described lubricant is in silicon dioxide, magnesium stearate, Pulvis Talci At least one.

As preferably, described clarithromycin also includes sweeting agent, and described sweeting agent is selected from from A Siba At least one in sweet, saccharin sodium.

As preferably, raw material and the part by weight of adjuvant described in step a be:

Clamycin 2 part, lactose 4 parts, starch 1.3 parts, crospolyvinylpyrrolidone 1 part, tristearin Acid 0.1 part of magnesium, Pulvis Talci 0.15 part, hydroxypropyl methyl cellulose 0.1 part, saccharin sodium 0.05 part

As preferably, the ethanol described in step b is 50% ethanol.

As preferably, pastille binding agent b step prepared and step c are prepared mixture and are put efficient wet system In grain machine, mixing speed 400rpm, the pelletize of shear rate 1000rpm are set, take out by 18-22 mesh sieve system Grain.

As preferably, the drying means described in step d is: fluid bed airpillow-dry, temperature of charge control 30 DEG C～ 60 DEG C, controlling moisture is 1.0%～3.0%.

As preferably, the total mixing method of granulate described in step d is: by the granule 20-25 after fluid bed drying Mesh sieve granulate, addition lubricant is put mix homogeneously in Mixers with Multi-direction Movement and is obtained midbody particle.

The invention has the beneficial effects as follows:

Due to the difficult soluble substance of clarithromycin tablet raw material, uniformity of dosage units, dissolution are clarithromycin tablets The index of major control, carries out pretreatment, energy by the method using the present invention to clarithromycin and binding agent Ensureing the medicament contg uniformity, reduce principal agent particle diameter simultaneously, raw material, without micronization, increases insoluble drug Dissolution, improve bioavailability, and common dissolving reduce technological operation step, save the energy and reduce and put into Cost.

Detailed description of the invention

Following embodiment is used for further illustrating but is not limited to the present invention.

The Selection experiment of embodiment 1 clarithromycin dissolution solvent

In taking raw material respectively about 200mg putting beaker, it is gradually added into variable concentrations (50%, 75%, 95%) Ethanol solution, shaking limit, limit is observed, until solution clarification, weighs added quantity of solvent.According to different ethanol The consumption of concentration, the mixed accessories to 800mg carries out soft material processed respectively, observes the humidity condition of soft material, and Carry out, with 20 mesh sieves, investigation of sieving, the results are shown in Table 1.

The selection of table 1 principal agent dissolution solvent and investigation result

Result: the ethanol solution of above-mentioned variable concentrations can dissolve 200mg raw material under a certain amount of very well, and it is molten Agent consumption has good wetting effect to 800mg adjuvant, and it has good formability to material particles, Determine this product granulation solvent employing 50～the ethanol solution of 95%.

Experimental example 2

The prescription of clarithromycin tablet one-tenth as shown in Table 2 is grouped into.

The prescription of table 2 clarithromycin tablet

The preparation method of above-mentioned clarithromycin is as follows:

Preparation technology:

1. by the clarithromycin of recipe quantity, hydroxypropyl methyl cellulose ultrasonic dissolution simultaneously in about 50g's In 75% ethanol solution, as the binding agent containing principal agent, this binding agent is water white transparency, gentle without agglomerate Bubble.

2. take the lactose of recipe quantity, corn starch, crospolyvinylpyrrolidone, saccharin sodium mixed 100 Mesh sieve 3 times.

3. the binding agent containing principal agent is joined in the mixture of step 2, prepare soft material 20 mesh sieve and pelletize, dry 60 DEG C of case is dried (moisture 1-3%).

4. granule crosses 24 mesh sieve granulate, and additional magnesium stearate mixes as midbody particle.

5. tabletting, tablet hardness scope control is 50～70N.

Experimental example 3

The prescription of clarithromycin tablet one-tenth as shown in Table 3 is grouped into.

The prescription of table 3 clarithromycin tablet

The preparation method of above-mentioned clarithromycin is as follows:

Preparation technology:

1. by the clarithromycin of recipe quantity, hydroxypropyl cellulose ultrasonic dissolution simultaneously in 50% second of about 70g In alcoholic solution, as the binding agent containing principal agent, this binding agent is water white transparency, without agglomerate and bubble.

2. take the lactose of recipe quantity, corn starch, cross-linking sodium carboxymethyl cellulose, aspartame mixed 100 mesh sieves 3 times.

3. the binding agent containing principal agent is joined in the mixture of step 2, prepare soft material 20 mesh sieve and pelletize, dry 40 DEG C of case is dried (moisture 1-3%).

5. tabletting, tablet hardness scope control is 50～70N.

Experimental example 4

The prescription of clarithromycin tablet one-tenth as shown in Table 4 is grouped into.

The prescription of table 4 clarithromycin tablet

The preparation method of above-mentioned clarithromycin is as follows:

Preparation technology:

1. by the clarithromycin of recipe quantity, hydroxypropyl cellulose ultrasonic dissolution simultaneously in 85% second of about 45g In alcoholic solution, as the binding agent containing principal agent, this binding agent is water white transparency, without agglomerate and bubble.

3. the binding agent containing principal agent is joined in the mixture of step 2, prepare soft material 20 mesh sieve and pelletize, dry 50 DEG C of case is dried (moisture 1-3%).

5. tabletting, tablet hardness scope control is 50～70N.

The clarithromycin present invention prepared grinds medicine contrast, the clarithromycin of the present invention with former With the former medicine that grinds in 0.1 hydrochloric acid solution, aqueous solution and pH4.5 buffer solution, pH6.8 phosphate buffer dissolution Dependence Results is shown in Table 5.

Table 5 is made sample (embodiment 1) by oneself and is ground commercially available product stripping curve measurement result with former

As can be seen from the table, clarithromycin tablet of the present invention self-control sample is in different dissolution mediums, not Under same time point, dissolution is above the former dissolution grinding medicine.

Claims

1. the preparation method of a clarithromycin, it is characterised in that: it comprises the steps:

A, the raw material weighing each weight proportion and adjuvant:

C, take filler, lubricant and disintegrant mixture and sieve, mixing；

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: described At least one in starch, dextrin, lactose, microcrystalline Cellulose of filler.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: described Binding agent selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, at least one Kind.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: described Disintegrating agent is selected from carboxymethylstach sodium, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose at least A kind of；At least one in silicon dioxide, magnesium stearate, Pulvis Talci of described lubricant.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: described Clarithromycin also includes sweeting agent, and described sweeting agent is selected from aspartame, saccharin sodium at least A kind of.

6. according to the preparation method of the clarithromycin described in claim 1, it is characterised in that: step a Described raw material and the part by weight of adjuvant be:

Clarithromycin 3 parts, lactose 5 parts, crospolyvinylpyrrolidone 0.1 part, magnesium stearate 0.15 part, Sodium carboxymethyl cellulose 0.05 part.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: step Ethanol described in b is 50% ethanol.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: step Method of granulating described in d is: pastille binding agent b step prepared and step c are prepared mixture and put high-efficiency wet In method granulator, mixing speed 400rpm, the pelletize of shear rate 1000rpm are set, take out and use 18-22 mesh Sieve series grain.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: step Drying means described in d is: fluid bed airpillow-dry, and temperature of charge controls 30 DEG C～60 DEG C, controls moisture Content is 1.0%～3.0%.

The preparation method of clarithromycin the most according to claim 1, it is characterised in that: step The rapid total mixing method of granulate described in d is: by the granule 20-25 mesh sieve granulate after fluid bed drying, add Lubricant is put mix homogeneously in Mixers with Multi-direction Movement and is obtained midbody particle.