CN104042578A - Domperidone orally disintegrating tablet and preparation method thereof - Google Patents

Abstract

The invention discloses a domperidone orally disintegrating tablet, which is reasonable in the formula and good in bioavailability, and a preparation method thereof. The domperidone orally disintegrating tablet comprises the following active ingredients in percentage by weight: main drug: 1%-5% of domperidone, and auxiliaries: a disintegrating agent, a dilution/adhesive, a binder, a sweetener, a flavoring agent, a lubricating agent and the like, the preparation method adopts a modern preparation technology, the domperidone orally disintegrating tablet is stable in quality, and the safe and effective domperidone orally disintegrating tablet can be provided for wide patients.

Description

A kind of domperidone orally disintegrating tablet and preparation method thereof

Invention field

The present invention relates to chemical pharmacy field, be specifically related to a kind of domperidone orally disintegrating tablet and preparation method thereof.

Background of invention

Because modern society rhythm of life is accelerated, the factors such as dietary structure change, the gastric motility crowd that lowly falls ill is increasing, and gastric motility lowly often causes the diseases such as functional dyspepsia, gastroesophageal reflux, and people are greatly affected quality of life.China's gastropathy sickness rate is approximately according to statistics number of the infected is about 300,000,000 people left and right, occupies first of the world.It is reported, gastrointestinal tract medication occupies the larger market share always, and world's gastrointestinal tract medicine annual sales amount is about 13,000,000,000 dollars, is the third-largest drug market.According to domestic Epidemiological study, find, in gastrointestinal special outpatient clinic patient, what relate to gastric motility problem accounts for 50%, and chronic gastritis sickness rate increases with the growth at age, and 50 years old above crowd can be up to since Xi'an Yang Sen introduces domestic market by third generation medicine for stomach dynamic-cisapride in 1993, medicine for stomach dynamic hospital market is fast-developing, has now become the important clinical application of domestic gastroenteropathy.

Domperidone (Doperidone) is as the representative of second filial generation medicine for stomach dynamic, it is a kind of synthetic benzimidazoles derivative, the chemoceptor trigger region of Main Function outside blood brain barrier, by blocking-up periphery dopamine receptor, thereby strengthen stomach and duodenal motion, the pressure that increases lower esophageal sphincter, is a kind of dopamine receptor-blocking agent with resisting emesis effect, the clinical treatment that is widely used in gastrointestinal distension, esophageal reflux and chemicotherapy patient nausea and vomiting.

The main conventional tablet of domestic existing domperidone preparation, there is no domperidone orally disintegrating tablet listing at present.

It is reasonable that the technical problem to be solved in the present invention is to provide a kind of formula, the domperidone orally disintegrating tablet that bioavailability is good.Another object of the present invention is to provide a kind of preparation method of domperidone orally disintegrating tablet agent, and it adopts modern technology of preparing, can commercial scale, high efficiency production, and it is stable that product quality keeps.

Summary of the invention

The object of the present invention is to provide a kind of eutherapeutic domperidone orally disintegrating tablet and preparation technology thereof, and through repetition test, each component screening is arrived to weight ratio of the present invention, be surprised to find that the tablet quality obtaining is stable, stripping is fast, in body, distribute rapidly, bioavailability is high.

On the one hand, the invention provides a kind of domperidone orally disintegrating tablet, comprise principal agent and adjuvant, wherein, the weight percent content of described principal agent domperidone is: 1%～5%.

Some embodiments therein, domperidone orally disintegrating tablet of the present invention, is characterised in that described adjuvant is by disintegrating agent, dilution/adhesive, binding agent, the compositions such as sweeting agent, aromatic, lubricant, its weight percent content is:

Disintegrating agent 5%～20%

Dilution/adhesive 50%～90%

Sweeting agent 1%～5%

Aromatic 0.5%～3%

Binding agent 1%～3%

Lubricant 0.5%～2%.

In other embodiment, domperidone orally disintegrating tablet of the present invention, wherein every 1000 are comprised of following weight item:

Domperidone 10g

Mannitol 750g

Crospolyvinylpyrrolidone 180g

Aspartame 30g

Fragrant citrus essence 15g

Polyvinylpyrrolidone 20g

Magnesium stearate 15g.

Some embodiments therein, domperidone orally disintegrating tablet of the present invention, wherein said dilution/adhesive is that mannitol, disintegrating agent are that crospolyvinylpyrrolidone, binding agent are polyvinylpyrrolidone, and sweeting agent is that aspartame, aromatic are that fragrant citrus essence, lubricant are magnesium stearate.

On the other hand, the present invention relates to a kind of preparation method of domperidone orally disintegrating tablet, its preparation process is as follows:

1) by domperidone raw material and dilution/adhesive, the premixing in three-phase granulator of part disintegrating agent;

2) in upper step mixed powder, add binding agent 50% alcohol-water solution to granulate;

3) wet granular is poured out rear stand dish, is placed in the interior 60'C thousand of baking oven dry;

4) the 26 order granulate that sieve;

5) granule sweeting agent, aromatic and residue disintegrating agent being obtained with previous step is poured in three-dimensional mixer and is mixed homogeneously, then adds mix lubricant;

6) mixed material is poured in the hopper of tablet machine, adjustment sheet weighs and pressure, and carrying out tabletting and keeping slice, thin piece hardness is 20～40N.

The domperidone orally disintegrating tablet that the present invention makes has the following advantages: 1) disintegration rate is fast, and bioavailability is good.2) taking convenience, can swallow by common dose, can be placed in water and takes after disintegrate again, can also not need to take medicine with water swallow, is particularly useful for the patient of old man, children's's dysphagia and the inconvenient person that fetches water and takes medicine convenience is provided.Separately when this tablet of preparation owing to having adopted certain method of improving preparation mouthfeel, improved the drug compliance of child patient, preferably resolve the problem of taking baby ' difficulty.3) intestinal is residual few, and side effect is low.

The specific embodiment

Below in conjunction with embodiment, further explain the present invention, but embodiment does not limit in any form to the present invention.

Embodiment 1

Domperidone 10g

Mannitol 750g

Crospolyvinylpyrrolidone 180g

Aspartame 30g

Fragrant citrus essence 15g

Polyvinylpyrrolidone 20g

Magnesium stearate 15g

Make 1000.

By domperidone raw material and mannitol, the premixing in three-phase granulator of partial cross-linked polyvinylpyrrolidone; In upper step mixed powder, add polyvinylpyrrolidone 50% alcohol-water solution to granulate; Wet granular is poured out rear stand dish, is placed in 60oC in baking oven and is dried 5 hours; 26 order granulate sieve; The granule that aspartame, fragrant citrus essence and residue crospolyvinylpyrrolidone are obtained with previous step is poured in three-dimensional mixer and is mixed 30 minutes, then adds magnesium stearate to mix 1～2 minute; Mixed material is poured in the hopper of tablet machine, adjustment sheet weighs and pressure, and carrying out tabletting and keeping slice, thin piece hardness is 20-40N; Two aluminum cold forming blister packages.

Embodiment 2

Domperidone 10g

Mannitol 500g

Crospolyvinylpyrrolidone 350g

Aspartame 30g

Fragrant citrus essence 10g

Polyvinylpyrrolidone 15g

Magnesium stearate 15g

Make 1000.

By domperidone raw material and mannitol, the premixing in three-phase granulator of partial cross-linked polyvinylpyrrolidone; In upper step mixed powder, add polyvinylpyrrolidone 50% alcohol-water solution to granulate; Wet granular is poured out rear stand dish, is placed in 60oC in baking oven and is dried 4 hours.26 order granulate sieve; The granule that aspartame, fragrant citrus essence and residue crospolyvinylpyrrolidone are obtained with previous step is poured in three-dimensional mixer and is mixed 30 minutes, then adds magnesium stearate to mix 1～2 minute; Mixed material is poured in the hopper of tablet machine, adjustment sheet weighs and pressure, and carrying out tabletting and keeping slice, thin piece hardness is 20～40N; Two aluminum cold forming blister packages.

Embodiment 3

Domperidone 10g

Mannitol 750g

Crospolyvinylpyrrolidone 150g

Aspartame 25g

Fragrant citrus essence 10g

PVPK30 g

Magnesium stearate 10g

Make 1000.

By domperidone raw material and mannitol, the premixing in three-phase granulator of partial cross-linked polyvinylpyrrolidone; In upper step mixed powder, add polyvinylpyrrolidone 50% alcohol-water solution to granulate; Wet granular is poured out rear stand dish, is placed in 60oC in baking oven and is dried 7 hours; Guo Sieve 26 order granulate; The granule that aspartame, fragrant citrus essence and residue crospolyvinylpyrrolidone are obtained with previous step is poured in three-dimensional mixer and is mixed 30 minutes, then adds magnesium stearate to mix 1～2 minute; Mixed material is poured in the hopper of tablet machine, adjustment sheet weighs and pressure, and carrying out tabletting and keeping slice, thin piece hardness is 20-40N; Two aluminum cold forming blister packages.

Biological test

(2) domperidone orally disintegrating tablet assay

With reference to high-efficient liquid phase technique (two appendix VD of Chinese Pharmacopoeia version in 2010), measure.According to the pharmaceutical preparation formula of embodiment 1, make the domperidone orally disintegrating tablet of 3 batches, its content is as shown in table 1.

Table 1 domperidone orally disintegrating tablet assay

Batch	Domperidone orally disintegrating tablet content (%)
		Batch 1	100.25
Batches 2	100.23
		Batches 3	100.19

As can be seen from Table 1, the content of domperidone orally disintegrating tablet requirement up to specification.

(3) the quality stability comparison of domperidone orally disintegrating tablet

Domperidone orally disintegrating tablet accelerated test: the domperidone orally disintegrating tablet of blister package is put under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% and placed six months, outcome quality is stable, disintegrate rapidly in 1 minute, indices is as shown in table 2.

Six months accelerated test testing results of table 2 domperidone orally disintegrating tablet

Inspection batch	Outward appearance	Disintegration (s)	Dispersing uniformity	Dissolution %	Content %
						Batch 1	White is smooth	39	Up to specification	100.37	100.26
Batches 2	White is smooth	38	Up to specification	100.39	100.30
						Batches 3	White is smooth	39	Up to specification	100.36	100.20

Claims (5)

1. a domperidone orally disintegrating tablet, comprises principal agent and adjuvant, and wherein, the weight percent content of described principal agent domperidone is: 1%～5%.

2. domperidone orally disintegrating tablet according to claim 1, wherein said adjuvant is by disintegrating agent, dilution/adhesive, binding agent, the compositions such as sweeting agent, aromatic, lubricant, its weight percent content is:

Disintegrating agent 5%～20%

Dilution/adhesive 50%～90%

Sweeting agent 1%～5%

Aromatic 0.5%～3%

Binding agent 1%～3%

Lubricant 0.5%～2%.

3. domperidone orally disintegrating tablet according to claim 2, wherein dilution/adhesive is that mannitol, disintegrating agent are that crospolyvinylpyrrolidone, binding agent are polyvinylpyrrolidone, and sweeting agent is that aspartame, aromatic are that fragrant citrus essence, lubricant are magnesium stearate.

4. according to the domperidone orally disintegrating tablet described in claim 1-3 any one, wherein every 1000 are comprised of following weight item:

Domperidone 10g

Mannitol 750g

Crospolyvinylpyrrolidone 180g

Aspartame 30g

Fragrant citrus essence 15g

Polyvinylpyrrolidone 20g

Magnesium stearate 15g.

5. a preparation method for the domperidone orally disintegrating tablet as described in claim l-4 any one, its preparation process is as follows:

1) by domperidone raw material and dilution/adhesive, the premixing in three-phase granulator of part disintegrating agent;

2) in upper step mixed powder, add binding agent 50% alcohol-water solution to granulate;

3) wet granular is poured out rear stand dish, is placed in the interior 60'C thousand of baking oven dry;

4) the 26 order granulate that sieve;

5) granule sweeting agent, aromatic and residue disintegrating agent being obtained with previous step is poured in three-dimensional mixer and is mixed homogeneously, then adds mix lubricant;

6) mixed material is poured in the hopper of tablet machine, adjustment sheet weighs and pressure, and carrying out tabletting and keeping slice, thin piece hardness is 20～40N.