CN1250217C - Bifendate oral disintegration tablet and its preparing process - Google Patents

Abstract

The present invention relates to a biphenyl dimethyl dicarboxylate orally disintegrating tablet and a preparation process thereof. The biphenyl dimethyl dicarboxylate orally disintegrating tablet can be used for treating chronic unresolved hepatitis accompanied by abnormal increase or chemical-caused increase of alanine aminotransferase (ALT). The present invention aims at making up for the preparation insufficiency of existing biphenyl dimethyl dicarboxylate preparation and providing a biphenyl dimethyl dicarboxylate orally disintegrating tablet and a preparation process thereof for all patients and medical workers; the biphenyl dimethyl dicarboxylate orally disintegrating tablet has the advantages of convenient use and rapid absorption and effect-taking. Biphenyl dimethyl dicarboxylate is used as raw material; using filling agent, disintegrating agent, corrigent, flow aid, lubricating agent, etc. as auxiliary materials; filling agents, disintegrating agents, corrigents, flow aid, lubricating agents, etc. are used as auxiliary materials; adhesives or coating materials can also be used according to different situations; appropriate quantity of effervescent agents can be added on specific situation; the orally disintegrating tablet is prepared by a specific preparation method and obtained after tabletting by tabletting machines. The orally disintegrating tablet of the present invention has the characteristics of good friability, rapid disintegration, good taste, no gravel feel, no need of specific production condition, low production cost, convenient carry, storage, transportation and use, etc.; most of all, the orally disintegrating tablet can be taken without water and takes effect quickly, and therefore, the present invention improves the patient's compliance and enhances the curative effect of the medicine.

Description

Bifendate oral disintegration tablet and preparation technology thereof

[technical field]

The present invention relates to a kind ofly can be used for treating that chronic persistent hepatitis raises unusually with alanine aminotransferase (ALT) or the bifendate oral disintegration tablet preparation of the diseases such as ALT rising that chemicals causes.

[background technology]

Bifendate falls the enzyme medicine for treatment hepatitis, is a kind of intermediate of synthetic schisandrin C.This product is oral to be alleviated the serum alanine aminotransferase that causes because of carbon tetrachloride and thioacetamide and raises, and this product can also strengthen liver detoxification function, alleviate the pathology damage of liver, promotes liver cell regeneration also to protect hepatocyte, thereby improves liver function.This product has certain curative effect to the improvement of hepatitis cardinal symptom such as pain in the hepatic region, weak, abdominal distention etc., but the change of hepatosplenomegaly is not had influence.Clinically be applicable to chronic persistent hepatitis and the unusual person of the long-term individual event paddy third aminoacid transferring enzyme.

The dosage form of existing bifendate preparation has: drop pill, hard capsule, tablet and suspension.

Because dosage form needs a large amount of water to send down when most of oral formulations are taken, this makes the patient of many old peoples, infant or dysphagia, water intaking inconvenience be difficult to take.Therefore, be necessary to prepare and take convenient dosage form to satisfy the multiple needs that clinical treatment and family use.

[summary of the invention]

The objective of the invention is to improve the deficiency of existing bifendate aspect peroral dosage form, provide a kind of taking convenience, absorption is rapid-action, bioavailability is high bifendate oral disintegration tablet preparation to extensive patients and medical personnel.Needn't drink water when the present invention relates to take, in the oral cavity, only need get final product rapid disintegrate or dissolving in tens seconds, can finish bifendate oral disintegration tablet of taking medicine and preparation method thereof with saliva hypopharynx.

One, prescription

Bifendate oral disintegration tablet of the present invention, by bifendate, filler, disintegrating agent, correctives, fluidizer, lubricant, the optional binding agent that exists, the optional effervescent that exists is formed, wherein, calculate with weight percentage, bifendate 5%～50%, filler 10%～80%, disintegrating agent 2%～35%, correctives 1%～40%, fluidizer 0.01%～5%, lubricant 0.3%～3%, binding agent 0～5%, effervescent 0～30% is characterized in that: described filler is mannitol and microcrystalline Cellulose, or mannitol and silicified microcrystalline cellulose (PROSOLV SMCC), described disintegrating agent is crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose (L-HPC).

Above-mentioned oral cavity disintegration tablet, wherein:

Binding agent is selected from starch, pregelatinized Starch, dextrin, maltodextrin, sucrose, arabic gum, gelatin, methylcellulose, carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone (PVP), alginic acid and alginate, xanthan gum, hydroxypropyl cellulose and hydroxypropyl emthylcellulose (HPMC), can use use also capable of being combined separately.

Correctives is selected from mannitol, xylitol, stevioside, lactose, fructose, sucrose, protein sugar, maltose alcohol, glycyrrhizin, Sodium Cyclamate, gelatin, aspartame, flavoring banana essence, flavoring pineapple essence, vanillin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, strawberry essence, citric acid, citric acid etc., can use use also capable of being combined separately.

Fluidizer is selected from micropowder silica gel, Pulvis Talci, Cab-O-sil, Arosil, hydrated sodium aluminosilicate etc., can use use also capable of being combined separately.

Lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, Polyethylene Glycol, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium laurylsulfate, magnesium laurylsulfate, Stepanol MG and Pulvis Talci etc., can use use also capable of being combined separately.

Effervescent is selected from the mixture of malic acid, citric acid or citric acid and sodium bicarbonate or sodium carbonate.

Wherein, described bifendate disintegrating tablet, bifendate 25.0g, mannitol 53.5g, microcrystalline Cellulose 5.0g, crospolyvinylpyrrolidone 8.0g, low-substituted hydroxypropyl cellulose 4.0g, polyvinylpyrrolidone K-300.5g, aspartame 1.0g, ginseng essence 1.0g, micropowder silica gel 1.0g, sodium stearyl fumarate 1.0g makes 1000 altogether.

Perhaps, described bifendate disintegrating tablet, bifendate 25.0g, mannitol 28.0g, silicified microcrystalline cellulose 5.0g, crospolyvinylpyrrolidone 10.0g, low-substituted hydroxypropyl cellulose 5.0g, polyvinylpyrrolidone K-30 0.5g, aspartame 1.0g, fragrant citrus essence 1.0g, micropowder silica gel 1.0g, sodium stearyl fumarate 1.0g, citric acid 12.5g, sodium bicarbonate 10.0g makes 1000 altogether.

Two, preparation method

The bifendate oral disintegration tablet that reaches of the present invention, its preparation method is a direct compression process, the manufacturer with preparation conventional tablet all can adopt.

Bifendate is tasteless, and the present invention adopts the direct flavoring of correctives.

Concrete preparation method is as follows:

The first step is pulverized bifendate, crosses 150 mesh sieves, and the reuse binding agent carries out wet granulation, after the oven dry, crosses 30 mesh sieves, and is standby;

Second step made the bifendate granule with correctives and the first step and takes by weighing according to quantity, and mix homogeneously is standby;

The 3rd step took by weighing filler, disintegrating agent, effervescent, fluidizer and mix homogeneously according to quantity, made evenly again with through second mixing of materials that goes on foot gained, and adding lubricant mixing is standby;

The 4th step gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.

[beneficial effect]

Tablet is a kind of conventional dosage forms, because of its steady quality, dosage accurately, take, easy to carry, mechanization degree is high, low one of the at present the most frequently used dosage form that becomes of production cost, but because of the tablet extrusion forming, disintegrate is slow, bioavailability is lower, and part patient swallows comparatively difficult, thereby promoting the use of to a certain extent of tablet is restricted.The oral administration solid quick releasing formulation becomes a focus, particularly oral cavity disintegration tablet of new drug development in recent years for this reason, because of its taking convenience, rapid-action, bioavailability is high, the good emphasis that becomes tablet exploitation of mouthfeel.

Oral cavity disintegration tablet is meant not to be needed water or only needs low amounts of water, need not to chew, and tablet places lingual surface, disintegrate rapidly after the chance saliva, or borrow and swallow power, medicine can be gone into the tablet of stomach onset.The characteristics of oral cavity disintegration tablet are that absorption is fast, bioavailability is high, and intestinal is residual few, and side effect is low, avoids liver first-pass effect etc.

According to the requirement of " formulation characteristic of oral cavity disintegration tablet and quality control meeting summary ", oral cavity disintegration tablet has essential leap than the disintegration rate of drop pill and ordinary tablet, and the disintegrate of oral cavity disintegration tablet generally in 30 seconds, is no more than 1 minute at most.

[specific embodiment]

For better explanation bifendate oral disintegration tablet of the present invention and preparation method thereof, as follows for two embodiment:

Embodiment one

One. prescription

1. raw material---bifendate 25.0g;

2. binding agent---polyvinylpyrrolidone K-30 0.5g;

3. filler---mannitol 53.5g;

Microcrystalline Cellulose 5.0g;

4. correctives---aspartame 1.0g;

Ginseng essence 1.0g;

5. disintegrating agent---crospolyvinylpyrrolidone 8.0g;

Low-substituted hydroxypropyl cellulose (L-HPC) 4.0g;

6. fluidizer---micropowder silica gel 1.0g;

7. lubricant---sodium stearyl fumarate 1.0g.

Gross weight 100g makes 1000 altogether.

Two. preparation method

1) get the bifendate raw material pulverizing, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;

2) with micropowder silica gel, ginseng essence, microcrystalline Cellulose and aspartame, cross 40 mesh sieves respectively, mix homogeneously adds the bifendate granule of having granulated again, and mix homogeneously is standby;

3) get mannitol, L-HPC and crospolyvinylpyrrolidone and cross 40 mesh sieves respectively, mix homogeneously will add and mix homogeneously through the raw material of flavoring again, adds sodium stearyl fumarate and mix homogeneously at last;

4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.

Embodiment two

One. prescription

1. raw material---bifendate 25.0g;

2. binding agent---polyvinylpyrrolidone K-30 0.5g;

3. effervescent---citric acid 12.5g;

Sodium bicarbonate 10.0g;

4. filler---mannitol 28.0g;

Silicified microcrystalline cellulose (PROSOLV  SMCC) 5.0g;

5. correctives---aspartame 1.0g;

Fragrant citrus essence 1.0g;

6. disintegrating agent---crospolyvinylpyrrolidone 10.0g;

Low-substituted hydroxypropyl cellulose (L-HPC) 5.0g;

7. fluidizer---micropowder silica gel 1.0g;

8. lubricant---sodium stearyl fumarate 1.0g.

Gross weight 100g makes 1000 altogether.

Two. preparation method

1) get bifendate and citric acid raw material and mix the back pulverizing, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;

2) get sodium bicarbonate and pulverize, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;

3) adjuvant that all the other are all is crossed mix homogeneously behind 40 mesh sieves respectively, adds the granule of having granulated again, and mix homogeneously is standby;

4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.

Disintegration that the sample of the foregoing description is measured and slice, thin piece hardness are as follows:

Embodiment	Disintegration (second)	Slice, thin piece hardness (newton)
			1 2	11-22 15-28	18-26 16-25

Claims (4)

1. bifendate oral disintegration tablet, by bifendate, filler, disintegrating agent, correctives, fluidizer, lubricant, the optional binding agent that exists, the optional effervescent that exists is formed, wherein, calculate with weight percentage, bifendate 5%～50%, filler 10%～80%, disintegrating agent 2%～35%, correctives 1%～40%, fluidizer 0.01%～5%, lubricant 0.3%～3%, binding agent 0～5%, effervescent 0～30% is characterized in that: described filler is mannitol and microcrystalline Cellulose, or mannitol and silicified microcrystalline cellulose, described disintegrating agent is crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose.

2. the described bifendate oral disintegration tablet of claim 1, wherein:

Described correctives is selected from one or more in xylitol, stevioside, glycyrrhizin, Sodium Cyclamate, aspartame, flavoring banana essence, flavoring pineapple essence, vanillin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, the strawberry essence;

Described fluidizer is selected from one or more in micropowder silica gel, Pulvis Talci, the hydrated sodium aluminosilicate;

Described lubricant is selected from one or more in magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, sodium stearyl fumarate, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium laurylsulfate, magnesium laurylsulfate, the Stepanol MG;

Described binding agent is selected from one or more in starch, pregelatinized Starch, dextrin, maltodextrin, sucrose, arabic gum, methylcellulose, carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone K-30, alginic acid or alginate, xanthan gum, hydroxypropyl cellulose and the hydroxypropyl emthylcellulose;

Described effervescent is the mixture of malic acid, citric acid or citric acid and sodium bicarbonate or sodium carbonate.

3. the described bifendate oral disintegration tablet of claim 1, wherein, bifendate 25.0g, mannitol 53.5g, microcrystalline Cellulose 5.0g, crospolyvinylpyrrolidone 8.0g, low-substituted hydroxypropyl cellulose 4.0g, polyvinylpyrrolidone K-300.5g, aspartame 1.0g, ginseng essence 1.0g, micropowder silica gel 1.0g, sodium stearyl fumarate 1.0g makes 1000 altogether.

4. the described bifendate oral disintegration tablet of claim 1, wherein, bifendate 25.0g, mannitol 28.0g, silicified microcrystalline cellulose 5.0g, crospolyvinylpyrrolidone 10.0g, low-substituted hydroxypropyl cellulose 5.0g, polyvinylpyrrolidone K-300.5g, aspartame 1.0g, fragrant citrus essence 1.0g, micropowder silica gel 1.0g, sodium stearyl fumarate 1.0g, citric acid 12.5g, sodium bicarbonate 10.0g makes 1000 altogether.