CN101461789A

CN101461789A - Technique for preparing metronidazole benzoate dispersible tablet

Info

Publication number: CN101461789A
Application number: CNA2008102230318A
Authority: CN
Inventors: 徐新盛
Original assignee: Individual
Current assignee: Individual
Priority date: 2008-09-26
Filing date: 2008-09-26
Publication date: 2009-06-24

Abstract

The invention discloses preparation technology for a metronidazole benzoate dispersing tablet, which takes metronidazole benzoate as a main component and is assisted with a proper amount of filling agent, disintegrant, adhesive and lubricating agent. The product has quick disintegration, quickly exerts curative effect in human bodies, provides more selections for clinicians and patients, particularly patients with dysphagia, and has better clinical application prospect.

Description

Technique for preparing metronidazole benzoate dispersible tablet

Technical field

The present invention relates to technique for preparing metronidazole benzoate dispersible tablet, particularly this product is an indissoluble water medicine, and making can be oral behind the dispersible tablet, takes after also can adding aqueous dispersion, and disintegrate is rapid, brings into play curative effect in vivo rapidly.

Background technology

Benzoic methyl nitroazole is by Britain May﹠amp; Baker, the nitroimidazoles medicine that the anaerobe resistant of new generation that Co. (prunus mume (sieb.) sieb.et zucc. Baker Co., Ltd) develops, protozoacide infect.Now in country's listing such as tens of English, method, moral, days etc., in November, 1993 this medicine be the infection essential drugs by The World Health Organization's approval.Clinical each section's control anaerobic infection (1), the gynecological of being used for: gynecological infection, trichomonal vaginitis, Gardner's vaginitis, pelvic infection etc.(2), Gastroenterology dept.: the antibiotic that abdominal cavity infection, clostridium difficile cause be correlated with enteritis, the relevant gastritis of deep and remote bacillus or the outer amebiasis of peptic ulcer, intestinal and intestinal.(3), cardiopulmonary section: intimitis, empyema, pulmonary abscess, anaerobe pneumonia etc.(4), surgery: the bone and the infection of joint, meningitis, brain abscess, skin soft-tissue infection may pollute in the prophylactic of operation, as colorectum cutaneous leishmaniasis, dracunculiasis, giardiasis etc. such as choose date for operation.(5) department of stomatology: periodontal infection.At present, the dosage form of listing mainly contains capsule and oral administration mixed suspension at home.

Nineteen ninety-five, Hebei Pharmaceutical Factory, Tianjin City at first succeeds in developing this product at home, developed the oral administration mixed suspension dosage form, at present, the domestic market mainly is benzoic methyl nitroazole capsule and benzoic methyl nitroazole oral administration mixed suspension, capsule and dry suspension belong to conventional oral solid formulation, this product is water-soluble hardly, suspensoid helps improving the stability of medicine in aqueous solution, be convenient to oral, but because the inhomogeneous dispersion of suspensoid Chinese medicine, the Unstable Systems that belongs to thermodynamics and kinetics, the solids generation sedimentation that floats on a liquid influences redispersion, and dosage is accurately unsuitable.The capsule advantage is often for example: patient takes medicine and complies with, the bioavailability height, can improve medicine stability, prescription and production technology are simple or the like, but some shortcomings are also arranged, for example be not suitable for child and domsiekte and be difficult for swallowing, the difficult crowd that perhaps takes medicine is difficult for swallowing.Dispersible tablet has taking convenience, absorption is fast, bioavailability is high and untoward reaction is little, and disintegration rate can be put into water soon and disperse the oral advantage in back.

Medicine finally always is used for human body with the form of preparation, and the quality of the quality of the pharmaceutical preparations will directly influence the performance of curative effect of medication.Medicine for poorly water-soluble, the speed limit process that stripping absorbs often, because benzoic methyl nitroazole is water-soluble hardly, ordinary tablet exists that dissolution rate is low, stripping waits problem inadequately fully, for improving the dissolving out capability of oral formulations, guarantee the inherent quality of pharmaceutical preparation, improve biological effectiveness, select the preparation benzoyl metronidazole dispersion tablets.

The characteristics of dispersible tablet are to meet the rapid disintegrate of water to become fine particle, and uniform particles is disperseed and can be by No. 2 sieves (24 order).Insoluble drug is made dispersible tablet, can obviously improve the dissolving out capability of medicine, for the pharmaceutics basis has been established in the raising of biological effectiveness.Dispersible tablet has obvious superiority than general tablet, taking convenience not only, and disintegrate and stripping are quick, and bioavailability is suitable with capsule with oral suspensions.

Dispersible tablet and conventional tablet, capsule are relatively, taking convenience (can be oral or add aqueous dispersion after take, also can chew or contain to suck and take), absorb fast, bioavailability is high and untoward reaction is little, disintegration rate can be put into water soon and disperse the oral advantage in back, be fit to the general crowd except that same, crowd and tourism and the crowd that goes on business to the ill group of child, the difficulty of taking medicine more can improve the compliance of patient's medication, guarantee the therapeutic effect of medicine.

Summary of the invention

The invention provides the preparation technology of benzoyl metronidazole dispersion tablets, disintegrate is rapid, brings into play curative effect in vivo rapidly, and for the difficult crowd that takes medicine, provides convenience.

The preparation technology of benzoyl metronidazole dispersion tablets:

1. at first principal agent benzoic methyl nitroazole, filler lactose are crossed 100 mesh sieves respectively.

With amylum pregelatinisatum, microcrystalline Cellulose, cross three kinds of adjuvants of lactose and the principal agent benzoic methyl nitroazole mixing of crossing 100 mesh sieves of 100 mesh sieves, add 5%PVP _K29/32Aqueous solution, the preparation soft material.

3.16 mesh sieve is granulated, 50 ℃～60 ℃ dryings, 14 mesh sieve granulate.

4. add disintegrating agent crospolyvinylpyrrolidone XL-10, magnesium stearate lubricant, mixing.

5. Φ 11.5mm stamping.

The technological design main points:

The adjuvant granularity is one of key factor of control dispersible tablet quality.In the formulation and technology, principal agent is crossed 100 mesh sieves, and the adjuvant lactose is crossed 100 mesh sieves, its objective is controlling particle size and mix homogeneously.

Make filler with amylum pregelatinisatum merely, the tablet easy-formation, friability is lower, but disintegrate is relatively poor; Along with increasing of lactose consumption, shorten disintegration relatively, but the friability of slice, thin piece increases gradually, and behind a plurality of prescription screenings, final prescription determines with three adjuvant use in conjunction, tablet disintegrating property, friability, hardness, etc. all meet the requirements.

Because the principal agent amount is higher in this product prescription, powder flowbility is relatively poor, thus can not select direct compression, and select wet granulation.

PVP XL-10 adds by interior: add=3:1 adds the quick disintegrate help tablet, to guarantee that the suspension that dispersible tablet forms after the disintegrate can be all by No. 2 screen clothes in water.

The specific embodiment:

Example one:

Prescription:

Benzoic methyl nitroazole 320.0g lactose 35.0g

Amylum pregelatinisatum 25.0g microcrystalline Cellulose 25.0g

Crospolyvinylpyrrolidone 30.0g magnesium stearate 4.0g

5% polyvinylpyrrolidone K29/32 aqueous solution is an amount of

Preparation technology:

A. recipe quantity principal agent benzoic methyl nitroazole 320.7g is crossed 100 mesh sieve, recipe quantity lactose 35g crosses 100 mesh sieves.

B. with recipe quantity amylum pregelatinisatum 25.0g, microcrystalline Cellulose 25.0g, cross 100 mesh sieves lactose 35g, in add crospolyvinylpyrrolidone (PVP XL-10) 22.5g and the principal agent benzoic methyl nitroazole mixing of crossing 100 mesh sieves, add 5%PVP _K29/32Aqueous solution, the preparation soft material.

C.16 mesh sieve is granulated, 50 ℃～60 ℃ dryings, 14 mesh sieve granulate.

D. add crospolyvinylpyrrolidone XL-107.5g, recipe quantity magnesium stearate 4.0g, mixing.

E. Φ 11.5mm stamping.

Example two:

Prescription:

Benzoic methyl nitroazole 320.0g lactose 45.0g

Amylum pregelatinisatum 35.0g microcrystalline Cellulose 30.0g

Crospolyvinylpyrrolidone 35.0g magnesium stearate 4.2g

5% polyvinylpyrrolidone K29/32 aqueous solution is an amount of

Preparation technology:

A. recipe quantity principal agent benzoic methyl nitroazole 321.5g is crossed 100 mesh sieve, recipe quantity lactose 45g crosses 100 mesh sieves.

B. with recipe quantity amylum pregelatinisatum 35.0g, microcrystalline Cellulose 30.0g, cross 100 mesh sieves lactose 45g, in add crospolyvinylpyrrolidone (PVP XL-10) 26.25g and the principal agent benzoic methyl nitroazole mixing of crossing 100 mesh sieves, add 5%PVP _K29/32Aqueous solution, the preparation soft material.

D. add crospolyvinylpyrrolidone XL-103.75g, recipe quantity magnesium stearate 4.2g, mixing.

E. Φ 11.5mm stamping.

Example three:

Prescription:

Benzoic methyl nitroazole 320.0g lactose 40.0g

Amylum pregelatinisatum 40.0g microcrystalline Cellulose 30.0g

Crospolyvinylpyrrolidone 30.0g magnesium stearate 4.6g

5% polyvinylpyrrolidone K29/32 aqueous solution is an amount of

Preparation technology:

A. recipe quantity principal agent benzoic methyl nitroazole 320.5g is crossed 100 mesh sieve, recipe quantity lactose 40g crosses 100 mesh sieves.

B. with recipe quantity amylum pregelatinisatum 30.0g, microcrystalline Cellulose 30.0g, cross 100 mesh sieves lactose 45g, in add crospolyvinylpyrrolidone (PVP XL-10) 30.0g and the principal agent benzoic methyl nitroazole mixing of crossing 100 mesh sieves, add 5%PVP _K29/32Aqueous solution, the preparation soft material.

D. add crospolyvinylpyrrolidone XL-10,10.0g, recipe quantity magnesium stearate 4.6g, mixing.

E. Φ 11.5mm stamping.

Claims

1, benzoyl metronidazole dispersion tablets is a main component with the benzoic methyl nitroazole, adds an amount of filler and disintegrating agent, and filler is selected from least a of starch, microcrystalline Cellulose, amylum pregelatinisatum, sucrose, lactose; Disintegrating agent is selected from least a of microcrystalline Cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, Di Qu Dai Kong propyl cellulose, cross-linking sodium carboxymethyl cellulose.

2, the described dispersible tablet of claim 1, a kind of mistake 100 mesh sieves during wherein benzoic methyl nitroazole and filler are selected.

3, the described dispersible tablet of claim 1, also comprise at least a in binding agent, the lubricant, binding agent is selected from polyvinylpyrrolidone aqueous solution, starch slurry, the hydroxypropyl cellulose aqueous solution at least a, lubricant is selected from stearic acid, at least a in magnesium stearate, Pulvis Talci, Polyethylene Glycol, the Stepanol MG.

4, the described dispersible tablet of claim 2, filler is lactose, amylum pregelatinisatum, microcrystalline Cellulose, lactose is crossed 100 mesh sieves.

5, the described dispersible tablet of claim 3, binding agent are that concentration range is 1～10% polyvinylpyrrolidone aqueous solution; Lubricant is a magnesium stearate.

6, the described dispersible tablet of claim 5, benzoic methyl nitroazole is a main component, and disintegrating agent is a polyvinylpolypyrrolidone, and filler comprises lactose and microcrystalline Cellulose and amylum pregelatinisatum; Binding agent is the polyvinylpyrrolidone aqueous solution of concentration range 5%; Lubricant is a magnesium stearate.

7, the preparation method of claim 5 dispersible tablet: wet granulation.

8, the preparation method of the described dispersible tablet of claim 1～7: recipe quantity benzoic methyl nitroazole, lactose behind the micronization are crossed 100 mesh sieves respectively, with the adjuvant mix homogeneously of recipe quantity, are binding agent system soft material with 5% polyvinylpyrrolidone aqueous solution, and 16 mesh sieves are granulated.50 ℃～60 ℃ dryings add the magnesium stearate mixing, Φ 11.5mm stamping.

9, right is wanted the preparation method of 8 described dispersible tablets, and the addition method of the disintegrating agent polyvinylpolypyrrolidone in the adjuvant of recipe quantity adds by interior: add=the 3:1 adding.