CN101618027B - Aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof - Google Patents
Aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof Download PDFInfo
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- CN101618027B CN101618027B CN2009100125805A CN200910012580A CN101618027B CN 101618027 B CN101618027 B CN 101618027B CN 2009100125805 A CN2009100125805 A CN 2009100125805A CN 200910012580 A CN200910012580 A CN 200910012580A CN 101618027 B CN101618027 B CN 101618027B
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Abstract
The invention provides an aceclofenac bi-layer osmotic pump controlled release tablet and a preparation method thereof, belongs to the technical field of medicinal preparation. The osmotic pump preparation comprises a tablet core containing aceclofenac and a semipermeable coating membrane which is coated outside the tablet core and provided with orifices, the tablet core comprises a drug layer containing aceclofenac and a boosting layer; wherein, the drug layer comprises the following components: 200mg of aceclofenac, 100mg-300mg of suspension, 10mg-50mg of osmotic stress active substance and 0.5 mg-2mg of lubricant; the boosting layer comprises 50mg-150mg of sweller and 5mg-30mg of osmotic stress active substance; the semipermeable coating membrane comprises the following components: 10g-20g of semipermeable high polymer material dissolved in 500ml of acetone and 2g-5g of water soluble pore former dissolved in 20ml of distilled water and the weight of the coating membrane is 5%-10% of the tablet core weight; laser or a power drill is used to drill the orifices on the drug-containing side of the coating tablet. The invention is characterized of less dosing frequency, convenient taking way, long lasting and stable curative effect and can be used to cure pains and inflammations caused by osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and the like.
Description
Technical field
The invention belongs to technical field of medicine, relate to aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof.
Background technology
Aceclofenac (aceclofenac) is the potent NSAID (non-steroidal anti-inflammatory drug) of a kind of new oral, chemistry 2-[(2 by name, the 6-Dichlorobenzene base) amino] the phenylacetyl ethoxyacetic acid, be used for the treatment of pain and inflammation that osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, rheumatic arthritis, chronic polyarthritis, concurrency osteoarthritis etc. cause.Aceclofenac is the derivant of diclofenac sodium, ooze out by the biosynthesis of the scorching pain of inhibition epoxidase reduction position prostaglandin and by inflammatory mediators such as inhibition lipoxygenase reduction leukotriene, Kallidin Is, alleviate the congested swelling of partial inflammatory reaction, tissue, the mediator that reduces inflammation causes the sensitization that inflammation causes pain, thereby produces anti-inflammatory and analgesic effect.1997 in Britain, U.S.'s listing first in Spain's listing in 1992.
At present relevant aceclofenac dosage form mostly is ordinary tablet, capsule etc., does not see the research report that relates to aceclofenac bi-layer osmotic pump controlled release tablets of the present invention.
The aceclofenac oral absorption is complete, and bioavailability reaches 99%, reaches the blood drug level peak value in 1.25-3 hour, and biological half-life is 4-4.3 hour.Clinically, the conventional dosage of aceclofenac is 200 milligrams of every days, divides and takes medicine for 2-3 time.The common oral preparation blood concentration fluctuation is big, and patient dependence is poor, is unfavorable for clinical treatment, develops the needs that its controlled release preparation once-a-day then meets clinical development.With osmotic pressure is the osmotic pump type controlled release preparation of main release power, owing to can keep constant permeable pressure head in the external design time in the tablet, provides constant release power for the medicine of meeting water dissolution or even suspendible in the tablet discharges with zero level.The constant release of medicine has been avoided the peak valley phenomenon of blood drug level in the body effectively, has reduced the drug side effect that causes because of peak concentration, has also improved patient's compliance simultaneously.
Summary of the invention
The objective of the invention is: aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof is provided, the constant release of the medicine in this controlled release tablet has been avoided the peak valley phenomenon of blood drug level in the body effectively, reduce the drug side effect that causes because of peak concentration, also improved patient's compliance simultaneously; And with the release of zero level speed, local concentration is lower, can reduce and the gastrointestinal tract mucous medication amount that directly contacts, and reduces GI irritation.
The present invention is achieved through the following technical solutions:
The present invention is by the label that contains aceclofenac and be wrapped in the semi-transparent coating membrane that label has drug release hole outward and form, described label consists of: aceclofenac 200mg, suspensoid 100mg～300mg, osmotic pressure active substance 10mg～50mg, lubricant 0.5mg～2mg; The boosting layer consists of: sweller 50mg～150mg, osmotic pressure active substance 5mg～30mg; Semi-transparent coating membrane consists of: semipermeable polymer material 10g～20g is dissolved in the 500ml acetone, and water solublity porogen 2g～5g is dissolved in the 20ml distilled water; Coating membrane weight is 5%～10% of label weight; Medicated layer side at coated tablet is played drug release hole with laser or power auger.
It is 100000～600000 polyoxyethylene and/or in polyvinylpyrrolidone and/or arabic gum and/or sodium alginate and/or the hypromellose one or more that described suspensoid is selected from molecular weight.
Described osmotic pressure active substance is selected from one or more in sodium chloride and/or potassium chloride and/or magnesium sulfate and/or sodium sulfate and/or sucrose and/or lactose and/or mannitol and/or the xylitol.
Described lubricant is selected from one or more in magnesium stearate and/or Pulvis Talci and/or the micropowder silica gel.
It is in 4000000～7000000 the polyoxyethylene one or more that described sweller is selected from molecular weight.
Described semipermeable polymer material is selected from one or more in cellulose acetate and/or ethyl cellulose and/or acrylic resin and/or polyoxyethylene and/or the polyvinyl alcohol.
It is in 1500～6000 the Polyethylene Glycol one or more that described porogen is selected from mean molecule quantity.
The preparation method of aceclofenac bi-layer osmotic pump controlled release tablets may further comprise the steps:
(1) aceclofenac, suspensoid, osmotic pressure active matter and lubricant are crossed 80 mesh sieves, take by weighing above material by recipe quantity, with medicated layer and boosting layer mix homogeneously respectively, powder directly suppress label;
(2) take by weighing semipermeable polymer material and water solublity porogen by recipe quantity, and be dissolved in respectively in the acetone and distilled water of recipe quantity, the two mix homogeneously forms coating solution, label is put in the coating pan with the certain pressure spray coating, the coating parameter is: spray velocity 5～6ml/min, 40 ℃ of kettle temperatures, coating pan rotating speed 45～50r/min puts in the air dry oven coated tablet to remove residual solvent after satisfying weightening finish;
(3) beat the hole that diameter is 0.5～1.0mm in the medicated layer side of coated tablet with laser or power auger, promptly get aceclofenac bi-layer osmotic pump controlled release tablets.
Chronic diseases such as aceclofenac treatment of arthritis need long-term prescription, and drug half-life is short, and common oral preparation needs frequent drug administration, and take 2-3 every day.After aceclofenac is prepared into osmotic pump controlled release tablet, only need medication 1 time every day, significantly improved patient's compliance, and reduced the rate of missing.Aceclofenac is a NSAID (non-steroidal anti-inflammatory drug), and major side effects is that gastrointestinal is stimulated.Sustained-release preparation is widely used in the generation that reduces gastrointestinal side effect, aceclofenac is prepared into osmotic pump controlled release tablet after, with the release of zero level speed, local concentration is lower, can reduce and the gastrointestinal tract mucous medication amount that directly contacts, and reduces GI irritation.
Description of drawings
Fig. 1 is that the cumulative in vitro of the aceclofenac bi-layer osmotic pump controlled release tablets of embodiment 1 discharged percent-time graph in 14 hours.
Fig. 2 is that the cumulative in vitro of the aceclofenac bi-layer osmotic pump controlled release tablets of embodiment 2 discharged percent-time graph in 14 hours.
Fig. 3 is that the cumulative in vitro of the aceclofenac bi-layer osmotic pump controlled release tablets of embodiment 3 discharged percent-time graph in 14 hours.
The specific embodiment
The label prescription:
Medicated layer
Aceclofenac 200mg
Polyoxyethylene 250mg
Sucrose 50mg
Magnesium stearate 1mg
The boosting layer
Polyoxyethylene 70mg
Lactose 15mg
Semi-transparent coating membrane prescription:
Cellulose acetate 20g
Polyethylene Glycol 4g
The solvent prescription of dissolving coating membrane material:
Acetone 500mL
Distilled water 20mL
Preparation technology:
With medicine, the molecular weight of recipe quantity is that 300000 polyoxyethylene, sucrose, magnesium stearate are crossed 80 mesh sieves, mix homogeneously, with the molecular weight of recipe quantity is that 7000000 polyoxyethylene, lactose are crossed 80 mesh sieves, and mix homogeneously uses and dashes twice pressurization for No. 11 and promptly get label.With cellulose acetate and mean molecule quantity is that 2000 Polyethylene Glycol is dissolved in acetone and the water respectively and mix homogeneously, with coating pan label is carried out coating, and weightening finish is 7%, coating finish the back in baking oven 40 ℃ solidified 12 hours.Promptly get aceclofenac bi-layer osmotic pump controlled release tablets in coated tablet medicated layer side with one 1.0 mm dia small delivery aperture of power auger preparation then.
The label prescription:
Medicated layer
Aceclofenac 200mg
Sodium alginate 200mg
Sodium chloride 40mg
Magnesium stearate 1mg
The boosting layer
Polyoxyethylene 90mg
Sodium chloride 10mg
Semi-transparent coating membrane prescription:
Ethyl cellulose 20g
Polyethylene Glycol 4g
The solvent prescription of dissolving coating membrane material:
Acetone 500mL
Distilled water 20mL
Preparation technology:
Medicine, sodium alginate, sodium chloride, the magnesium stearate of recipe quantity are crossed 80 mesh sieves, and mix homogeneously is that 4000000 polyoxyethylene, sodium chloride are crossed 80 sieves with the molecular weight of recipe quantity, and mix homogeneously uses promptly to get label towards twice pressurization No. 11.With ethyl cellulose and mean molecule quantity is that 6000 Polyethylene Glycol is dissolved in acetone and the water respectively and mix homogeneously.With coating pan label is carried out coating, weightening finish is 8%, coating finish the back in baking oven 40 ℃ solidified 12 hours.Prepare one 0.8 mm dia small delivery aperture in coated tablet medicated layer side with power auger then and promptly get aceclofenac bi-layer osmotic pump controlled release tablets.Embodiment 3
The label prescription:
Medicated layer
Aceclofenac 200mg
Arabic gum 150mg
Mannitol 10mg
Micropowder silica gel 2mg
The boosting layer
Polyoxyethylene 140mg
Lactose 25mg
Semi-transparent coating membrane prescription:
Cellulose acetate 12g
Polyethylene Glycol 4g
The solvent prescription of dissolving coating membrane material:
Acetone 500mL
Distilled water 20mL
Preparation technology:
80 sieves are crossed in medicine, arabic gum, mannitol, the micropowder silica gel of recipe quantity, and mix homogeneously is that 5000000 polyoxyethylene, lactose are crossed 80 mesh sieves with the molecular weight of recipe quantity, and mix homogeneously uses promptly to get label towards twice pressurization No. 12.With cellulose acetate, acrylic resin and mean molecule quantity is that 4000 Polyethylene Glycol is dissolved in acetone and the water respectively and mix homogeneously, carries out coating with the coating pan label, and weightening finish is 8%, the coating back 40 ℃ of curing 12 hours in baking oven that finishes.Prepare one 0.6 mm dia small delivery aperture in coated tablet medicated layer side with power auger then and promptly get aceclofenac bi-layer osmotic pump controlled release tablets.
Embodiment 4:
The cumulative in vitro drug release determination of aceclofenac bi-layer osmotic pump controlled release tablets
According to " two drug release determination method first methods of The People's Republic of China's pharmacopeia version in 2005, release medium is a 900mL pH7.4 phosphate buffer, rotating speed 100rmin
-1, medium temperature (37 ± 0.5) ℃.Respectively at 2,4,6,8,10,12 and 14h sampling 5mL, replenish equal-volume equality of temperature release medium simultaneously.Suitably diluting after crossing 0.8 μ m microporous filter membrane, is blank with the release medium, measures trap in the 275nm place, calculates the cumulative release degree.
Accompanying drawing 1, what Fig. 2 and Fig. 3 represented respectively is according to embodiment 1, the cumulative in vitro of the aceclofenac bi-layer osmotic pump sheet of example 2 and example 3 preparations discharged percent-time graph in 14 hours, though the result shows the present invention and makes the mono-layer osmotic pump preparation for insoluble drug, but the aceclofenac release is complete, has reached more than 80%.
Claims (3)
1. aceclofenac bi-layer osmotic pump controlled release tablets, it is by the label that contains aceclofenac and be wrapped in the semi-transparent coating membrane that label has drug release hole outward and form, and it is characterized in that:
Described label is made up of medicated layer and boosting layer, and every medicated layer consists of: aceclofenac 200mg, suspensoid 100mg～300mg, osmotic pressure active substance 10mg～50mg, lubricant 0.5mg～2mg; The boosting layer consists of: sweller 50mg～150mg, osmotic pressure active substance 5mg～30mg;
Per 100 of described semi-transparent coating membrane consists of: semipermeable polymer material 10g～20g is dissolved in the 500ml acetone, and water solublity porogen 2g～5g is dissolved in the 20ml distilled water; Coating membrane weight is 5%～10% of label weight;
Described drug release hole is in the medicated layer side of sheet, and the aperture is 0.5mm～1.0mm;
It is 100000～600000 polyoxyethylene and/or in polyvinylpyrrolidone and/or arabic gum and/or sodium alginate and/or the hypromellose one or more that described suspensoid is selected from molecular weight;
Described osmotic pressure active substance is selected from one or more in sodium chloride and/or potassium chloride and/or magnesium sulfate and/or sodium sulfate and/or sucrose and/or lactose and/or mannitol and/or the xylitol;
It is in 4000000～7000000 the polyoxyethylene one or more that described sweller is selected from molecular weight;
Described semipermeable polymer material is selected from one or more in cellulose acetate and/or ethyl cellulose and/or acrylic resin and/or polyoxyethylene and/or the polyvinyl alcohol;
It is in 1500 ~ 6000 the Polyethylene Glycol one or more that described water solublity porogen is selected from mean molecule quantity.
2. aceclofenac bi-layer osmotic pump controlled release tablets according to claim 1 is characterized in that: described lubricant is selected from one or more in magnesium stearate and/or Pulvis Talci and/or the micropowder silica gel.
3. the preparation method of an aceclofenac bi-layer osmotic pump controlled release tablets as claimed in claim 1 is characterized in that: may further comprise the steps:
(1) with the medicated layer composition: aceclofenac, suspensoid, osmotic pressure active matter and lubricant and boosting composition of layer: suspensoid, osmotic pressure active matter are crossed 80 mesh sieves respectively, take by weighing above material by recipe quantity, mix homogeneously, with powder directly suppress label;
(2) take by weighing semipermeable polymer material and water solublity porogen by recipe quantity, and be dissolved in respectively in the acetone and distilled water of recipe quantity, the two mix homogeneously forms coating solution, label is put in the coating pan with the certain pressure spray coating, the coating parameter is: spray velocity 5～6ml/min, 40 ℃ of kettle temperatures, coating pan rotating speed 45～50r/min puts in the air dry oven coated tablet to remove residual solvent after satisfying weightening finish;
(3) beat the hole that diameter is 0.5～1.0mm in a side of coated tablet medicated layer with laser or power auger, promptly get aceclofenac bi-layer osmotic pump controlled release tablets.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100125805A CN101618027B (en) | 2009-07-16 | 2009-07-16 | Aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof |
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| CN2009100125805A CN101618027B (en) | 2009-07-16 | 2009-07-16 | Aceclofenac bi-layer osmotic pump controlled release tablets and preparation method thereof |
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| CN101618027B true CN101618027B (en) | 2013-07-31 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102198112A (en) * | 2010-03-26 | 2011-09-28 | 北京天衡药物研究院 | Osmotic pump type controlled release tablets and preparation method thereof |
| CN103816131B (en) * | 2012-11-16 | 2015-09-09 | 沈阳药科大学 | Flurbiprofen double-layer osmotic pump controlled-release tablet and preparation method thereof |
| WO2023284724A1 (en) * | 2021-07-12 | 2023-01-19 | 上海博志研新药物技术有限公司 | Sacubitril valsartan sodium sustained-release composition, and preparation method therefor and use thereof |
| CN114306260B (en) * | 2021-12-29 | 2023-10-24 | 濮阳市汇元药业有限公司 | Novel diclofenac sodium tablet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1622799A (en) * | 2001-01-30 | 2005-06-01 | 科学和工业研究委员会 | Pharmaceutical composition for sustained or continuous releasing therapeutic active components |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1622799A (en) * | 2001-01-30 | 2005-06-01 | 科学和工业研究委员会 | Pharmaceutical composition for sustained or continuous releasing therapeutic active components |
Non-Patent Citations (5)
| Title |
|---|
| 双氯芬酸钠缓释微丸胶囊的制备;吴宁苹等;《中国现代应用药学杂志》;20010831;第18卷(第4期);第290-292页 * |
| 口服缓控释制剂研究进展及临床应用;朱兰等;《现代预防医学》;20081231;第35卷(第10期);第1983-1985页 * |
| 吴宁苹等.双氯芬酸钠缓释微丸胶囊的制备.《中国现代应用药学杂志》.2001,第18卷(第4期),第290-292页. |
| 唐星.渗透泵型控释制剂.《口服缓控释制剂》.人民卫生出版社,2007,(第1版),第208-212页. * |
| 朱兰等.口服缓控释制剂研究进展及临床应用.《现代预防医学》.2008,第35卷(第10期),第1983-1985页. |
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