CN105267166A - Preparation method of domperidone composition - Google Patents
Preparation method of domperidone composition Download PDFInfo
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- CN105267166A CN105267166A CN201410349817.XA CN201410349817A CN105267166A CN 105267166 A CN105267166 A CN 105267166A CN 201410349817 A CN201410349817 A CN 201410349817A CN 105267166 A CN105267166 A CN 105267166A
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- domperidone
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- autoclave
- polymer beads
- supercritical fluid
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Abstract
The invention belongs to the technical field of medicine, and particularly relates to a preparation method of a domperidone pharmaceutical composition; through application of a supercritical fluid crystallization technology, copolymer particles of domperidone and accessories are prepared, so as to improve the bioavailability and the curative effect of a drug, avoid use of a surfactant and reduce toxic and side effects of the drug.
Description
Technical field
The present invention relates to a kind of preparation method of domperidone compositions, belong to field of pharmaceutical preparations.
Background technology
Domperidone, the chloro-1-of 5-[1-[3-(2,3-dihydro-2-oxo--1H-benzimidazole-1-base) propyl group] piperidin-4-yl]-1,3-dihydro-2H-2-ketone benzimidaozole, the dopamine-receptor antagonist that a kind of effect is stronger, there is periphery retardation, directly act on gastrointestinal arm, lower esophageal sphincter tension force can be increased, prevent stomach-esophageal regurgitation, strengthen gastric peristalsis, promote gastric emptying, coordinate stomach and uodenal movement, suppress Nausea and vomiting and effectively can prevent bile reflux, not affecting gastric secretion.Be applicable to the indigestion caused by gastric emptying, gastroesophageal reflux, esophagitis, sense as swollen in epigastrium, abdominal distention, Upper abdominal pain, belch, flatulence, the stomach burn feeling of with or without gastric content reflux in Nausea and vomiting, mouth.Still can treat functional, organic, infectious, caused by Diet, radiation treatment or chemotherapy Nausea and vomiting etc.
Usually we improve the dissolubility of water-insoluble medicine by reducing granularity, but, reduce granularity and can effectively not make the raising of the dissolution rate of medicine reach certain value needed.Many water-insoluble medicines are strongly tending towards agglomerating into larger particles and reducing total effective surface area in dosage form manufacturing process.
Crystalization in supercritical fluid technology prepares the new method of micron medicine, its principle utilizes supercritical fluid to spray as carbon dioxide etc. mixes from nozzle in the supercritical state with drug solution, micron order microgranule is formed in tens microseconds, by regulating the parameters such as pressure, temperature, flow, concentration, drug particle size, crystal formation can be controlled.Crystalization in supercritical fluid technology can also make medicine and high polymer adjuvant form micron order composite particles, ensure that the dissolubility of medicine, thus ensure that the curative effect of medicine, and composite particles has good crystal stability.Therefore, crystalization in supercritical fluid technology has become the technology platform preparing new formulation.
Summary of the invention
The object of the invention is the copolymer pellet by using crystalization in supercritical fluid technology to prepare domperidone and adjuvant, thus improve bioavailability and the curative effect of medicine, avoid using surfactant, reduce the toxic and side effects of medicine.
The invention provides a kind of preparation method of pharmaceutical composition, the copolymer pellet wherein containing domperidone, antioxidant and hydrophilic high molecular material composition, this comprises following several step:
(1) domperidone, antioxidant and hydrophilic high molecular material solution is prepared: domperidone, antioxidant and hydrophilic high molecular material are dissolved in ethanol and oxolane (4: 1) mixed solvent completely, obtain solution, solution temperature is 20-60 DEG C;
(2) feed carbon dioxide: inputted in the autoclave of crystalization in supercritical fluid equipment system by pressure-regulating valve by the carbon dioxide in steel cylinder, flow is 0.2-10ml/min; The temperature that controls environment is 20-80 DEG C, and pressure is 10-130MPa;
(3) polymer beads is separated out: spray in autoclave by above-mentioned solution through the nozzle of crystalization in supercritical fluid equipment system, polymer beads is separated out and is collected in the bottom of autoclave from solution; The diameter of described nozzle is 0.5-3mm;
(4) polymer beads will obtained, adds other excipient, is prepared into tablet further.
In the present invention in polymer beads the amount of domperidone in 1-20% (weight), preferred 5-10%.
The hydrophilic high molecular material used in the present invention is optional from polyvinylpyrrolidone, polyvinyl alcohol, hypromellose, hydroxypropyl cellulose or its mixture.
Hydrophilic high molecular material accounts for composition weight 5-10%.
Antioxidant is selected from sodium sulfite, sodium pyrosulfite, malic acid, tartaric acid, ascorbic acid, butylhydroxy anisole or its mixture.
Antioxidant accounts for the 0.5-3% of composition weight.
Any excipient being generally used for medicine and chemical field can also be included according to the present composition, this excipient is compatible with effective ingredient, as binding agent, wetting agent, disintegrating agent, correctives etc., such as can be used for excipient of the present invention has: microcrystalline Cellulose, lactose, mannitol, pregelatinized Starch, magnesium stearate, polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose sodium, Pulvis Talci, micropowder silica gel etc.
Detailed description of the invention
The following example is used for explaining further or understanding content of the present invention, but can not limit the scope of the invention.
Embodiment 1:
| Composition | Percentage ratio % |
| Domperidone | 5 |
| Hypromellose E5 | 10 |
| Ascorbic acid | 2 |
| Mannitol | 41.5 |
| Microcrystalline Cellulose | 40 |
| Magnesium stearate | 1.5 |
(1) by domperidone, hypromellose E5, dissolution of ascorbic acid in ethanol and oxolane (4: 1) mixed solvent, obtain solution, solution temperature is 50 DEG C;
(2) inputted in the autoclave of crystalization in supercritical fluid equipment system by pressure-regulating valve by the carbon dioxide in steel cylinder, flow is 1.2ml/min; The temperature that controls environment is 50 DEG C, and pressure is 100MPa;
(3) polymer beads is separated out: spray in autoclave by above-mentioned solution through the nozzle of crystalization in supercritical fluid equipment, polymer beads is separated out and is collected in the bottom of autoclave from solution; The diameter of described nozzle is 1mm;
(4) polymer beads will obtained, additional mannitol, microcrystalline Cellulose, magnesium stearate, be pressed into tablet further.
Embodiment 2:
| Composition | Percentage ratio % |
| Domperidone | 10 |
| Hypromellose E5 | 10 |
| Butylhydroxy anisole | 0.5 |
| L-TARTARIC ACID | 0.5 |
| Lactose | 43 |
| Microcrystalline Cellulose | 30 |
| Cross-linking sodium carboxymethyl cellulose | 5 |
| Magnesium stearate | 1 |
(1) domperidone, hypromellose E5, butylhydroxy anisole, L-TARTARIC ACID are dissolved in ethanol and oxolane (4: 1) mixed solvent, obtain solution, solution temperature is 40 DEG C;
(2) inputted in the autoclave of crystalization in supercritical fluid equipment system by pressure-regulating valve by the carbon dioxide in steel cylinder, flow is 0.8ml/min; The temperature that controls environment is 50 DEG C, and pressure is 100MPa;
(3) polymer beads is separated out: spray in autoclave by above-mentioned solution through the nozzle of crystalization in supercritical fluid equipment, polymer beads is separated out and is collected in the bottom of autoclave from solution; The diameter of described nozzle is 1mm;
(4) polymer beads will obtained, additional lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate, be pressed into tablet further.
Embodiment 3:
| Composition | Percentage ratio % |
| Domperidone | 10 |
| Hypromellose E5 | 10 |
| Ascorbic acid | 2 |
| Butylhydroxy anisole | 0.5 |
| Lactose | 21.5 |
| Microcrystalline Cellulose | 20 |
| Cross-linking sodium carboxymethyl cellulose | 35 |
| Magnesium stearate | 1 |
(1) domperidone, hypromellose E5, ascorbic acid, butylhydroxy anisole are dissolved in ethanol and oxolane (4: 1) mixed solvent, obtain solution, solution temperature is 30 DEG C;
(2) inputted in the autoclave of crystalization in supercritical fluid equipment system by pressure-regulating valve by the carbon dioxide in steel cylinder, flow is 1.0ml/min; The temperature that controls environment is 50 DEG C, and pressure is 100MPa;
(3) polymer beads is separated out: spray in autoclave by above-mentioned solution through the nozzle of crystalization in supercritical fluid equipment, polymer beads is separated out and is collected in the bottom of autoclave from solution; The diameter of described nozzle is 2mm;
(4) polymer beads will obtained, additional lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate, be pressed into tablet further.
Claims (4)
1. a preparation method for domperidone compositions, is characterized in that comprising the steps:
1) domperidone, antioxidant and hydrophilic high molecular material solution is prepared: domperidone, antioxidant and hydrophilic high molecular material are dissolved in completely in ethanol and oxolane (4: 1) mixed solvent, obtain solution;
2) feed carbon dioxide: the carbon dioxide in steel cylinder is inputted by pressure-regulating valve in the autoclave of crystalization in supercritical fluid equipment system;
3) polymer beads is separated out: spray in autoclave by above-mentioned solution through the nozzle of crystalization in supercritical fluid equipment system, polymer beads is separated out and is collected in the bottom of autoclave from solution;
4) polymer beads will obtained, adds other excipient, is prepared into tablet further.
2. method according to claim 1, is characterized in that step 1) in solution temperature be 20-60 DEG C.
3. method according to claim 1, is characterized in that step 2) in carbon dioxide flow be 0.2-10ml/min.
4. method according to claim 1, is characterized in that step 3) described in the diameter of nozzle be 0.5-3mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410349817.XA CN105267166A (en) | 2014-07-21 | 2014-07-21 | Preparation method of domperidone composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410349817.XA CN105267166A (en) | 2014-07-21 | 2014-07-21 | Preparation method of domperidone composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105267166A true CN105267166A (en) | 2016-01-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410349817.XA Pending CN105267166A (en) | 2014-07-21 | 2014-07-21 | Preparation method of domperidone composition |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060078573A1 (en) * | 2004-06-11 | 2006-04-13 | Theodore Randolph | Methods of modifying crystal habit |
| CN1850079A (en) * | 2006-02-27 | 2006-10-25 | 南京长澳医药科技有限公司 | Micro-powder dom peridone maleate medicinal composition and its preparing method |
| CN101152156A (en) * | 2006-09-29 | 2008-04-02 | 上海爱的发制药有限公司 | Domperidone orally disintegrating tablets and method for preparing the same |
| CN102106823A (en) * | 2010-12-24 | 2011-06-29 | 国家纳米技术与工程研究院 | Resveratrol composite fine particle preparation process applying supercritical fluid crystallization technology |
-
2014
- 2014-07-21 CN CN201410349817.XA patent/CN105267166A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060078573A1 (en) * | 2004-06-11 | 2006-04-13 | Theodore Randolph | Methods of modifying crystal habit |
| CN1850079A (en) * | 2006-02-27 | 2006-10-25 | 南京长澳医药科技有限公司 | Micro-powder dom peridone maleate medicinal composition and its preparing method |
| CN101152156A (en) * | 2006-09-29 | 2008-04-02 | 上海爱的发制药有限公司 | Domperidone orally disintegrating tablets and method for preparing the same |
| CN102106823A (en) * | 2010-12-24 | 2011-06-29 | 国家纳米技术与工程研究院 | Resveratrol composite fine particle preparation process applying supercritical fluid crystallization technology |
Non-Patent Citations (4)
| Title |
|---|
| 俞慧群等: "6家多潘立酮片的溶出度考察", 《中国药师》 * |
| 夏怡然等: "纳米药物晶体的制备技术研究进展", 《中国医药工业杂志》 * |
| 张杨等: "超临界流体结晶技术研究进展", 《化工科技》 * |
| 胡爱军等: "超临界流体结晶技术及其应用研究", 《化工进展》 * |
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Application publication date: 20160127 |