CN1319533C - Cefetamet pivoxil hydrochloride dispersion dispersion tablets and preparation method - Google Patents

Abstract

The present invention relates to a cefetamet pivoxil hydrochloride dispersion tablet and a preparation method thereof. The dispersion tablet comprises 25 to 35 wt% of active components, 55 to 70 wt% of filling agents, 2.0 to 5.0 wt% of disintegrating agents, 1.0 to 2.0 wt% of corrigent, 0.5 to 2.0 wt% of lubricating agents and 0.2 to 0.4 wt% of adhesives. The preparation method adopts the boiling granulation technology, and simultaneously, auxiliary materials are added to be mixed so as to press a tablet. The technology is simple, the operation is easy, and the product quality is stable. The dispersion tablet can rapidly and uniformly dissolve in water, has the advantages of convenient administration and high absorption speed, and is especially suitable for infants and patients who have difficulty in swallowing food.

Description

Hydrochloric acid cefetamet pivoxil dispersible tablet and preparation method thereof

Technical field

The present invention relates to pharmaceutical composition and preparation method thereof, a kind of hydrochloric cefetamet pivoxil dispersible tablet is used for respiratory tract infection and urinary system infection.

Background technology

The oral third generation cephalosporin medicine that Cefetamet Pivoxil Hydrochloride system is developed in late 1970s by Japan's military field Pharmaceutical and Switzerland Hoffmann Roche company, its structural formula is:

Molecular formula: C ₂₀H ₂₅N ₅O ₇HCL molecular weight: 548.04

Chemical name is: (6R, 7R)-the 3-methyl-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)-acetylamino]-8-oxo-5-thia-1-azabicyclo [4,2,0] oct-2-ene-2-formic acid pivaloyl oxygen methyl ester hydrochloride.

First in Mexico's listing, dosage form was a tablet to this product, specification 500mg/ sheet, trade name Globocef in 1992.Behind this medicine oral administration by intestinal absorption and the very fast cefetamet that antibacterial activity is arranged that become by the intestinal walls esterase hydrolyzed.Cefetamet is a broad-spectrum antibiotic, and gram positive bacteria and negative bacterium are all had effect, especially Diplococcus pneumoniae, hemophilus influenza, Klebsiella etc. is had very strong antibacterial activity.Stable to various beta-lactamases.This medicine clinical efficacy is remarkable, and adverse reaction rate is low, and patient tolerability is good, not only is applicable to the adult, also is applicable to old man and infant.This medicine extensive use clinically at present, domestic also existing several families introduce this product to the market, and the preparation variety of listing has tablet (125mg, 250mg, 500mg), capsule (125mg), and dry suspension (125mg).

It is bigger that Cefetamet Pivoxil Hydrochloride conventional tablet, capsule remove volume, is unsuitable for infant and swallows outside the patient that has any problem takes, and capsule softgel shell changeableness very in the long term storage process delays to absorb and release in vitro in the body simultaneously.Also need control uniform temperature and humidity in the production process, to prevent that softgel shell is softening and to become fragile.Conventional tablet because the Cefetamet Pivoxil Hydrochloride flavor is very bitter, generally need will be taken behind the sheet pericardium clothing, complex process, and all there is the problem that stripping is slow, onset is slow in these two kinds of dosage forms.Though the suspensoid taking convenience still needs certain condition control in production, storing process.Therefore the needs searching is a kind of had both made things convenient for the patient to take, rapid-action again, also will be convenient to the Cefetamet Pivoxil Hydrochloride preparation of production and transport.

As everyone knows, dispersible tablet is to put into water, and be that disintegratable disperses to be the homogeneous suspension a moment, and taking convenience absorbs rapidly the oral solid formulation that bioavailability is high.

Summary of the invention

The purpose of this invention is to provide a kind of hydrochloric acid cefetamet pivoxil dispersible tablet and preparation method thereof, this dispersible tablet taking convenience, fast, the long term storage steady quality of absorption, preparation technology is simple, and above-mentioned variety of issue is readily solved.

Hydrochloric acid cefetamet pivoxil dispersible tablet of the present invention comprises active component and adjuvant, it is characterized in that each set of dispense ratio is: (% by weight percentage)

Effective active composition 25-35

Filler 58-70

Disintegrating agent 2.0-5.0

Correctives 1.0-2.0

Lubricant 0.5-1.0

Binding agent 0.2-0.4

The preparation method of preparation: it is characterized in that adopting boiling granulating preparation technology; principal agent is sieved, puts into the boiling granulating machine drum body after the weighing; the binding agent that sprays into dilution is granulated, drying; add filler, disintegrating agent, correctives and lubricant; mix homogeneously; tabletting can obtain every dispersible tablet that contains effective composition 125-250mg.

Hydrochloric acid cefetamet pivoxil dispersible tablet of the present invention is to adopt boiling granulating technology, principal agent is made granule earlier after, mix tabletting with other adjuvants again.Its advantage is:

1, improves product stability

Cefetamet Pivoxil Hydrochloride raw material viscosity is strong excessively among the present invention, and under hot and humid condition the chemical property instability.If adopt wet granulation technology, not only be difficult to make granule, and in dry (generally at 50 ℃, the 2 hours) process of granulating, contained active component is easy to degraded.And adopting boiling granulating technology, granulation to carry out simultaneously with drying, baking temperature only needs 30-40 ℃, and can finish in 10-20 minute, has improved product stability.

2, improve the product content uniformity

Among the present invention in the particulate preparation process of Cefetamet Pivoxil Hydrochloride, the adhesive viscosities that adopts is little, concentration is low, earlier former medicine is made the particle diameter smaller particles, be evenly distributed, good fluidity, it is strong to have overcome in the dry method direct compression technology this active component viscosity, mobile poor, and the principal agent tablet weight variation that proportion causes greatly in prescription is big, and slice, thin piece content is difficult for uniform problem.

3, production efficiency height

Hydrochloric acid cefetamet pivoxil dispersible tablet of the present invention is to adopt boiling granulating technology, and granulation, dry run are carried out in the machine bucket of sealing simultaneously, have reduced powder and have flown upward, and help labor protection, and drying time is short, the production efficiency height.

4, good absorbing

Disintegrate and stripping are the speed limit processes of oral solid formulation, thereby the disintegrate and the dissolution rate of raising insoluble medicine are particularly important.Though Cefetamet Pivoxil Hydrochloride is an insoluble medicine in this dispersible tablet, but owing in this dispersible tablet, added super-disintegrant and good excipient, therefore this product put into water 20-30 second rapidly disintegrate become homodisperse fine particle, the whole strippings of principal agent 2 minutes time of taking medicine.And conventional tablet, capsule need be taken all strippings after 30 minutes, therefore preparation method of the present invention is carrier with the dispersible tablet with Cefetamet Pivoxil Hydrochloride, make it have conventional tablet, incomparable disintegrate and the dissolving out capability of capsule, it is fast to take post-absorption, the bioavailability height.

5, taking convenience

The hydrochloric acid cefetamet pivoxil dispersible tablet available water is taken after mixing it with water, also it can be contained in suck in the mouth clothes or swallow.Because of having added bitterness masking agent and fruit essence, taste is suitable in this invention product, therefore not only is fit to the adult and uses, and also is fit to infant and uses, and has good compliance in the clinical use.

The specific embodiment

The set of dispense ratio of hydrochloric acid cefetamet pivoxil dispersible tablet is: (% by weight percentage)

Embodiment 1 g %

Effective active composition Cefetamet Pivoxil Hydrochloride 125 26.8

Filler microcrystalline Cellulose 320 68.7

Binding agent hypromellose 1.0 0.21

Disintegrating agent polyvinylpolypyrrolidone 10 2.1

Magnesium stearate lubricant 3 0.6

Preparation method: 1, the preparation of binding agent (1): measure water 100ml, add hypromellose 1.0g, stir and make its dissolving.

2, particulate preparation: after Cefetamet Pivoxil Hydrochloride crossed 120 mesh sieves, take by weighing 125g and put and spray into binding agent (1) in the boiling granulating machine drum body, carry out boiling granulating, dried granule is through 30 mesh sieve granulate.

3, preparation tablets: add the 320g microcrystalline Cellulose, the 10g polyvinylpolypyrrolidone, 5g bitterness masking agent, 2g Herba Menthae essence and 3g magnesium stearate, mix homogeneously is made 1000, the 466mg/ sheet; Hydrochloric Ro-15-8075 125mg/ sheet.

Example 2:g %

Effective active composition Cefetamet Pivoxil Hydrochloride 200 34.1

Filler pregelatinized Starch 345 58.9

Binding agent hypromellose 2.0 0.34

Disintegrating agent cross-linking sodium carboxymethyl cellulose 25 4.3

Magnesium stearate lubricant 3 0.51

1, the preparation of binding agent (2): measure water 100ml, add hypromellose 2.0g, stir and make its dissolving

2, particulate preparation: after Cefetamet Pivoxil Hydrochloride crossed 120 mesh sieves, take by weighing 200g and put and spray into binding agent (2) in the boiling granulating machine drum body, carry out boiling granulating, dried granule is through 30 mesh sieve granulate.

3, the preparation of tablet: add pre-paying of 345g starch, the 25g cross-linking sodium carboxymethyl cellulose, 9g bitterness masking agent, 2g Herba Menthae essence and 3g magnesium stearate, mix homogeneously is made 1000, the 586mg/ sheet; Hydrochloric Ro-15-8075 200mg/ sheet.

Example 3:g %

Effective active composition Cefetamet Pivoxil Hydrochloride 250 30.5

Binding agent polyvidone 3.0 0.37

Magnesium stearate lubricant 8 0.98

The preparation of binding agent (3): measure water 100ml, add polyvidone 3.0g, stir and make its dissolving.

1, particulate preparation: take by weighing 250g after his U.S. ester of hydrochloric acid head sieved, put in the boiling granulating machine drum body, spray into binding agent (3), carry out boiling granulating, dried granule is through 30 mesh sieve granulate.

2, the preparation of tablet: add the 400g microcrystalline Cellulose, 120g calcium hydrogen phosphate, 15g polyvinylpolypyrrolidone, 10g carboxymethylstach sodium, the 10g aspartame, 4g Herba Menthae essence and 8g magnesium stearate, mix homogeneously, make 1000, the heavy 820mg of sheet, hydrochloric Ro-15-8075 250mg/ sheet.

Detect: the hydrochloric acid cefetamet pivoxil dispersible tablet that the present invention is made has carried out external dispersion, dissolution and stability test, has carried out the dissolution contrast test with the like product cefetamet pivoxil hydrochloride capsule simultaneously.Result of the test shows, product disintegrate of the present invention, stripping are rapid, steady quality.

Test method:

1, dispersivity test: 2 of products of the present invention are placed the jolting of 100ml water, in 20 ± 1 ℃ of water, disintegrate fully in 3 minutes, and can cross No. 2 and sieve (2000 editions two appendix IA of Chinese Pharmacopoeia).

2, dissolution test: adopt Chinese Pharmacopoeia appendix XC dissolution determination method second method, dissolution medium: 0.1molHCl, 900ml, rotating speed: 75 rev/mins, temperature: 37 ° ± 2 ℃.Timing sampling 10ml uses the 0.8um membrane filtration, replenishes fresh medium 10ml: adopt ultraviolet spectrophotometry to detect this filtrate, absorbing wavelength is 263nm, measures its trap, according to criterion keying method, calculates different time accumulation stripping percentage rate.It the results are shown in Table I, Table II, shown in data be all three batch data meansigma methodss.

3, stability test: product adopts two aluminum packings, under 40 ± 2 ℃ of RH:75 ± 5% condition, placed 6 months, placed 24 months under 25 ± 2 ℃ of RH:60 ± 5% condition, difference is indexs such as sampling and measuring sample size, related substance, dispersing uniformity, dissolution at the appointed time.Result of the test sees Table III, Table IV.

By Table I, Table II as seen, the hydrochloric acid cefetamet pivoxil dispersible tablet dissolution rate is significantly better than cefetamet pivoxil hydrochloride capsule, and accumulation stripping percentage rate can reach 100% in the time of 2 minutes.By Table III, Table IV as seen, this constant product quality is placed 2 years every indexs for a long time and is not had significant change.

Table I hydrochloric acid cefetamet pivoxil dispersible tablet stripping data

Time (branch)	2	5	10	20	30
						Accumulative total stripping percentage rate (%)	102.7	102.7	103.2	102.4	103.2

Table II: cefetamet pivoxil hydrochloride capsule stripping data

Time (branch)	2	5	10	20	30
						Accumulative total stripping percentage rate (%)	0	18.1	72.7	90.6	99.4

Cefetamet pivoxil hydrochloride capsule is Dongbei Pharmaceutical General Factory production, lot number 20030402,20020403,20020405

Table III: hydrochloric acid cefetamet pivoxil dispersible tablet accelerated stability test result of the test (40 ± 2 ℃ of RH:75 ± 5%)

Time (moon)	Character	Moisture (%)	Related substance (%)	Dissolution (%)	Content (%)
						0	Yellowish color chips	4.17	1.37	100.0	97.0
1	Yellowish color chips	4.20	1.57	99.5	96.2
						2	Yellowish color chips	4.05	1.30	99.6	96.7
3	Yellowish color chips	4.29	1.30	100.4	96.2
						6	Yellowish color chips	4.15	1.28	101.4	96.9

Table IV: the hydrochloric acid cefetamet pivoxil dispersible tablet result of the test (25 ± 2 ℃ of RH:60 ± 5%) that keeps sample for a long time

Time/moon	Character	Moisture (%)	Related substance (%)	Dissolution (%)	Content (%)
						0	Yellowish color chips	4.17	1.37	100.0	97.0

3	Yellowish color chips	4.06	1.38	100.0	96.4
						6	Yellowish color chips	4.12	1.34	98.7	96.5
12	Yellowish color chips	4.13	1.32	98.6	96.4
						24	Yellowish color chips	4.10	1.31	98.5	96.4

Usage: the hydrochloric acid cefetamet pivoxil dispersible tablet available water is taken after mixing it with water, also it can be contained in suck in the mouth clothes or swallow.Be dissolved in tablet in an amount of warm water and rock 2-3 minute to all dissolvings, it is oral to drink pharynx.

Usual amounts: oral in ante cibum or 1 hour after meal, adult and the child more than 12 years old, each 500mg, every day 2 times; Child below 12 years old, each per kilogram of body weight 10mg, every day 2 times; The adult of complexity urinary tract infection, every day, all dosage was taken in 1 hour after supper, the patient of the urethritis of male gonococcus and women's non-complex cystitis takes in regard to 1 hour after the meal, and single dose 1500-2000mg (cystitis person between the lights) is eradication of pathogens fully.

Claims (4)

1, a kind of hydrochloric acid cefetamet pivoxil dispersible tablet, the percentage by weight that it is characterized in that raw material consists of: active component: Cefetamet Pivoxil Hydrochloride 25-35%, filler: microcrystalline Cellulose or microcrystalline Cellulose and calcium hydrogen phosphate 63.4-70%, or pregelatinized Starch 58.9%; Disintegrating agent: polyvinylpolypyrrolidone and carboxymethylstach sodium 3.0%, or cross-linking sodium carboxymethyl cellulose 4.3%, or polyvinylpolypyrrolidone 2.1%; Correctives: 1.0-2.0%; Lubricant: magnesium stearate 0.5-2.0%, binding agent: hypromellose 0.2-0.4% or polyvidone 0.37%, correctives can adopt in Herba Menthae essence, bitterness covering agent, the aspartame one or more; Each composition sum is 100% in the dispersible tablet.

2, a kind of dispersible tablet as claimed in claim 1 is characterized in that the percentage by weight of dispersible tablet raw material of each specification is composed as follows:

1： g ％

Effective active composition 125 26.8

Filler microcrystalline Cellulose 320 68.7

Binding agent hypromellose 1.0 0.21

Disintegrating agent polyvinylpolypyrrolidone 10 2.1

Magnesium stearate lubricant 3 0.6

2：

Effective active composition Cefetamet Pivoxil Hydrochloride 200 34.1

Filler pregelatinized Starch 345 58.9

Binding agent hypromellose 2.0 0.34

Disintegrating agent cross-linking sodium carboxymethyl cellulose 25 4.3

Magnesium stearate lubricant 3 0.51

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