CN100350909C - Method for preparing insoluble drug single-tablet-core single-chamber osmotic pump sustained-release preparations and its product - Google Patents
Method for preparing insoluble drug single-tablet-core single-chamber osmotic pump sustained-release preparations and its product Download PDFInfo
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Abstract
The present invention provides a preparation method of a single tablet core single-chamber osmotic pump controlled release formulation of insoluble medicine and a product thereof. In the method, the insoluble medicine is loaded on a low-molecular sugar osmotic agent by a dissolvant dispersing method, the low-molecular sugar osmotic agent generates a solubilization function to the insoluble medicine at the same time of dissolving step by step and generating osmotic pressure to promote the release of the medicine, and consequently, the problems that a single tablet core single-chamber osmotic pump can not completely release and the linear of a release degree is poor are solved. Satisfactory linear release to the insoluble medicine can be obtained by the method.
Description
Technical field
The present invention relates to preparation method of a kind of controlled releasing penetrant pump and products thereof, relate in particular to preparation method of a kind of insoluble drug single-tablet-core single-chamber oral osmotic pump controlled release formulation and products thereof.
Background technology
Divided primary osmotic pump and " plug-type " osmotic pumps by business-like Oros preparation, the latter has the double-layer tablet cored structure of medicated layer and push layer, the push layer chance water of being made up of high molecular polymer and osmotically active component can expand, medicated layer after the promotion aquation, thus medicine is progressively discharged.But double-deck label need adopt twice tabletting of special equipment to finish, and need make two-layer obvious difference with colorant, with the laser instrument of apparatus color recognition function after finishing the release-controlled film coating at medicated layer one STH.Obviously, above-mentioned whole production complex process and technical difficulty are big, and production control point is many, has increased the quality control difficulty, are difficult to large-scale production.Though and the primary osmotic pump preparation has the simple structure of single chamber monolayer label, be convenient to produce, but be considered to only be suitable in water, having the medicine of certain solubility, be insoluble in the medicine of water for this non-dissociative type of similar felodipine, discharging homogeneity and discharging not exclusively is the main problem that this class osmotic pump preparation is used.
Many known technology are used to promote the dissolving of insoluble medicine, for example make its micronization, form solid dispersion, with cyclodextrin inclusion compound etc.Patent CN1189774A has proposed to form solid dispersion with hydrophilic poloxamer and felodipine, but it needs the hydrophilic adjuvant of several times amount to carry out the preparation of medicine under the hot melt condition.Patent CN1341451A adopts beta-schardinger dextrin-that insoluble medicine is formed clathrate, and with the solubility of solution monolithic core osmotic pump insoluble medicine, but clathrate needs more beta-schardinger dextrin-, and only making, the last sheet of osmotic pump tablet of pastille 5mg weighs more than the 640mg.Patent US5736159 and US5837379 have described a kind of monolithic core osmotic pump of nifedipine, it is dissolved in the insoluble medicine nifedipine in 2 times of polyvinyl pyrrolidones (povidone) more than the amount with acetone and isopropyl alcohol in advance, then in fluid bed with granulations such as osmotically active agent sodium chloride and filler microcrystalline Cellulose, 90% dry back granule adds nearly 9% extender polyethylene glycol oxide and 1% magnesium stearate fine powder carries out tabletting, makes the monokaryon label.The extender polyethylene glycol oxide that this arts demand is a large amount of, it meets the wet water generation property change of meeting, and influences drug release, and the outer add mode of a large amount of fine powders employing, and the tabletting process is brought the production control difficulty.Patent US6814979 does not adopt the component with expansion function when preparing the monolithic core osmotic pump of insoluble drug nifedipine, reach the release of medicine by the solubilising component, but the rate of release linearity is relatively poor.
Hence one can see that, and the method for osmotic pump preparation for preparing insoluble drug at present is perfect not enough, therefore, need to seek a kind of method of osmotic pump preparation of new preparation insoluble drug, discharge to obtain better linearity, and simplify production technology, reduce production costs.
Summary of the invention
The objective of the invention is to, a kind of preparation method of insoluble drug single-tablet-core single-chamber osmotic pump sustained-release preparations is provided, thus solved single-tablet-core single-chamber osmotic pump be difficult to discharge fully and the linear relatively poor problem of release.For insoluble drug, adopt this method can obtain satisfied linearity and discharge.
Method of the present invention is that insoluble drug is carried on low molecular saccharides penetrating agent in the solvent dispersion mode, and this low molecular saccharides penetrating agent is when self progressively dissolves and produces osmotic pressure, and the effect to insoluble medicine produces solubilising promotes the release of medicine.With this medicine carrying penetrating agent and other make medicine be easy to discharge or the adjuvant for preparing according to a conventional method wet granulation, tabletting, wrap the release-controlled film clothing again, and on coated tablet, punch, can obtain the single-tablet-core single-chamber osmotic pump controlled release agent of insoluble drug.
The preparation method of the single-tablet-core single-chamber osmotic pump sustained-release preparations of a kind of insoluble drug provided by the invention may further comprise the steps:
1) insoluble drug is dissolved in the organic solvent, the weight ratio of described organic solvent and insoluble drug is 5: 1 to 20: 1;
2) step 1) gained solution and low molecular saccharides penetrating agent are fully mixed, in 40-60 ℃ of optional vacuum drying, grind resulting mixture then, the low molecular saccharides mixture of medicine that obtained load;
3) with step 2) the low molecular saccharides mixture of gained with help suspensoid, extender and other adjuvants to mix after, be prepared into single-tablet-core single-chamber osmotic pump sustained-release preparations according to conventional method.
In the step 1) of the present invention, the selection of described organic solvent should determine that should select the little solvent of easy dissolved substance and toxicity, the consumption of solvent is unsuitable excessive, but should guarantee that medicine can dissolve fully according to pharmaceutical properties.This kind solvent should comprise the alcohols of (1) small-molecular weight, as methanol, ethanol, isopropyl alcohol etc., preferably ethanol and isopropyl alcohol; (2) ketone of small-molecular weight is as acetone; (3) halogenated alkane of small-molecular weight, commonly used is chloroform and carbon tetrachloride etc.Organic solvent can be selected from one or more in above-mentioned.The weight ratio of described organic solvent and insoluble drug is preferably 10: 1.
In addition, in the step 1), can adopt one or more following measures to promote the dissolving of insoluble drug: to add 5 times surfactant, heating or supersound process being no more than drug weight; Described surfactant is selected from one or more in polyvinylpyrrolidone, polyethylene glycols, Tween 80, castor oil hydrogenated, sodium lauryl sulphate or the Stepanol MG.
Insoluble drug of the present invention can be dihydropyridine type calcium antagonists antihypertensive medicine or sulfonylurea hypoglycemic drug, and the example of this compounds comprises felodipine or glipizide.
Step 2 of the present invention) in, described low molecular saccharides penetrating agent is selected from one or more in lactose, sucrose, fructose, glucose or the mannitol; The weight ratio of low molecular saccharides penetrating agent and insoluble drug is 5: 1 to 50: 1, is preferably 10: 1 to 25: 1.With respect to the inorganic salt penetrating agent, the affinity interaction of low molecular saccharides penetrating agent and water-insoluble medicine is stronger, more helps reducing the surface tension of drug solution, and medicine is loaded on the low molecular saccharides more equably; And after solvent evaporates, the effect of similar " hydrogen bond " also can take place in the functional groups such as hydroxyl on low molecular saccharides surface, reduces self gathering of drug molecule, thereby better dispersion medicine promotes solubilization.
Step 2) in, step 1) gained solution and low molecular saccharides penetrating agent are fully mixed,, grind resulting mixture then and cross 100 mesh sieves, the low molecular saccharides mixture of medicine that obtained load in 40-60 ℃ of drying.Described drying also can adopt vacuum drying.
In the step 3) of the present invention, described extender is selected from one or more in poly(ethylene oxide), arabic gum, sodium alginate or the pregelatinized starch, and the weight ratio of extender and insoluble drug is 1: 10～1: 1, is preferably 1: 5.These extenders help making insoluble medicine to be linear, to discharge completely.The consumption of the extender among the present invention is employed in the double-layer osmotic pump tablet, and the main component of the promoting layer in the double-layer osmotic pump tablet is exactly an extender.
Employed helping can be dissolved in the water of suspensoid under 37 ℃ or most of dissolving among the present invention, and can make the water thickening and produce the suspendible effect that disperses fine particles.The described suspensoid that helps can be selected from soluble starch, sodium carboxymethyl cellulose, hypromellose, dextrin, Polyethylene Glycol or the gelatin one or more.Helping the weight ratio of suspensoid and insoluble drug is 2: 1 to 10: 1, is preferably 5: 1.
Available sodium chloride, potassium chloride are further regulated the osmotic pressure of preparation, to reach the rate of release of expectation.
In the step 3) of the present invention, with step 2) the low molecular saccharides mixture of gained with help suspensoid, extender and other adjuvants to mix after, can be prepared into single-tablet-core single-chamber osmotic pump sustained-release preparations according to conventional method.Comprising wet granulation, tabletting, bag release-controlled film clothing, adopt that again laser instrument punches etc. on coated tablet.Other used adjuvants in the present invention's preparation comprise filler, binding agent, lubricant and relevant osmotic pumps semipermeable membrane coating etc., are this area adjuvant commonly used.Above conventional method and adjuvant commonly used can be referring to " novel form of medicine and new technique " (Lu Bin chief editor, People's Health Publisher) and " pharmaceutic adjuvant is used complete works of " (pharmaceutical preparation portion of Shanghai Institute of Pharmaceutical Industry write, Chinese Medicine science and technology publishing house) etc.
The preparation method of the single-tablet-core single-chamber osmotic pump sustained-release preparations of insoluble drug provided by the invention has the following advantages: (1) is easy and simple to handle, need not special manufacturing process and equipment, with respect to micronization, has very significantly cost advantage; (2) with respect to preparation solid dispersion, cyclodextrin inclusion compound etc., this method is also easier, and running cost is lower; (3) the used low molecular saccharides of solubilising itself is penetrating agent, need not to increase other special adjuvants, and is therefore also less on cost of supplementary product; Simultaneously, also can make the osmotic pump tablet of reduced size, make things convenient for the patient to take; (4) can reach better linearity and discharge, and can be near 100% release fully.
Description of drawings
Fig. 1 is the release profiles of embodiment one and two prepared felodipine osmotic pump controlled release tablets.
Fig. 2 is the release profiles of embodiment three and four prepared glipizide osmotic pump controlled release tablets.
The specific embodiment
Below in conjunction with specific embodiment and relevant drawings, the present invention is carried out detailed explanation.But, below the embodiment that provided just for the present invention is described, be not limitation of the present invention.
Embodiment one:
The felodipine osmotic pump controlled release tablet
(1) label prescription (1000 consumptions)
Composition g
Load the low molecular saccharides mixture 65 of felodipine
(containing felodipine 5g)
Sodium chloride 45
Poly(ethylene oxide) 2
Tween 80 5
Polyvinylpyrrolidone 6
Magnesium stearate 0.75
(2) label preparation
5g felodipine raw material (can be in crystal type, unformed and both mixed types any) is dissolved in the alcohol solvent that is dissolved with the recipe quantity Tween 80 by 1: 5 weight ratio.Take by weighing sucrose 65g, the solution that will contain felodipine adds, and stirs fast 30 minutes, put baking oven in 55 ℃ dry down, the low molecular saccharides mixture of felodipine that obtained load.
With above-mentioned load the low molecular saccharides mixture of felodipine fully mix with all the other adjuvants of recipe quantity, add an amount of ethanol after wet method make granule, add tabletting behind the magnesium stearate lubricant, promptly get label.
(3) preparation of osmotic pump controlled release tablet:
With weight ratio is that 9: 1 cellulose acetate (acetyl base value 39.8%) and PEG4000 is dissolved in chloroform and methanol (volume ratio 2: the 1) mixed solution, is mixed with the coating solution of solid content (solid content is the percentage composition that soluble solids accounts for coating (molten) liquid) 3%.To the label coating, about 4～6% in coating pan to increasing weight, with coated tablet 55 ℃ dry down, about coated tablet, both sides respectively open one 0.4～0.6mm aperture with laser instrument, promptly.
(4) mensuration of release
Measure the cumulative release amount (method is 2005 editions two appendix XD first methods of Chinese Pharmacopoeia, and rotating speed is that per minute 75 changes) of felodipine in containing the phosphate buffered solution of 0.5% sodium lauryl sulphate pH6.8, measurement result as shown in Figure 1.
Embodiment two:
The felodipine osmotic pump controlled release tablet
(1) label prescription (1000 consumptions)
Composition g
Load the low molecular saccharides mixture 60 of felodipine
(containing felodipine 5g)
Potassium chloride 65
Dextrin 20
Arabic gum 8
Polyethylene Glycol-6,000 15
Castor oil hydrogenated 3
Polyvinylpyrrolidone 6
Magnesium stearate 0.75
(2) label prepares 5g felodipine raw material (can be in crystal type, unformed and both mixed types any) and is dissolved in the isopropanol solvent (including recipe quantity Polyethylene Glycol-6000 and castor oil hydrogenated) by 1: 4 weight ratio, take by weighing mannitol 55g, the solution that will contain felodipine adds, stirred 30 minutes fast, put baking oven in 55 ℃ down dry, the low molecular saccharides mixture of felodipine that obtained load.
With above-mentioned load the low molecular saccharides mixture of felodipine fully mix with all the other adjuvants of recipe quantity, add an amount of ethanol after wet method make granule, add tabletting behind the magnesium stearate lubricant, promptly get label.
(3) osmotic pump controlled release tablet preparation and drug release determination are with embodiment one.
Embodiment three:
The glipizide osmotic pump controlled release tablet
(1) label prescription (1000 consumptions)
Composition g
Load the low molecular saccharides mixture 105 of glipizide
(containing glipizide 5g)
Soluble starch 30
Poly(ethylene oxide) 1
Polyvinylpyrrolidone 6
Magnesium stearate 0.75
(2) label prepares 5g glipizide raw material (can be in crystal type, unformed and both mixed types any) and is dissolved in chloroform/acetone (3: 1) mixed solvent by 1: 4 weight ratio, take by weighing lactose 50g, sucrose 50g by weight, the solution that will contain glipizide after mixing adds, stirred 30 minutes fast, put baking oven in 55 ℃ down dry, the low molecular saccharides mixture of glipizide that obtained load.
With above-mentioned load the low molecular saccharides mixture of glipizide fully mix with all the other adjuvants of recipe quantity, add an amount of ethanol after wet method make granule, add tabletting behind the magnesium stearate lubricant, promptly get label.
(3) the osmotic pump controlled release tablet preparation is with embodiment one.
(4) drug release determination is measured the cumulative release amount (method is 2005 editions two appendix XD first methods of Chinese Pharmacopoeia, and rotating speed is that per minute 75 changes) of glipizide in the phosphate buffered solution of pH7.4, and measurement result as shown in Figure 2.
Embodiment four:
The glipizide osmotic pump controlled release tablet
(1) label prescription (1000 consumptions)
Composition g
Load the low molecular saccharides mixture 75 of glipizide
(containing glipizide 5g)
Poly(ethylene oxide) 6
PEG-6000 10
Polyvinylpyrrolidone 6
Magnesium stearate 0.75
(2) label prepares 5g glipizide raw material (can be in crystal type, unformed and both mixed types any) and is dissolved in chloroform/acetone (3: 1) mixed solvent by 1: 4 weight ratio, take by weighing fructose 70g, the solution that will contain glipizide adds, stirred 30 minutes fast, put baking oven in 55 ℃ down dry, the low molecular saccharides mixture of glipizide that obtained load.
With above-mentioned load the low molecular saccharides mixture of glipizide fully mix with all the other adjuvants of recipe quantity, add an amount of ethanol after wet method make granule, add tabletting behind the magnesium stearate lubricant, promptly get label.
(3) the osmotic pump controlled release tablet preparation is with embodiment one.
(4) drug release determination is with embodiment three.
Those of ordinary skills do not depart from generalized invention essence of the present invention to many changes and improvements that the foregoing description carried out as can be known.Therefore can think, the invention is not restricted to above-mentioned preferred embodiment, and be intended to comprise any all improvement in the determined protection domain of claims of the present invention.
Claims (8)
1. the preparation method of the single-tablet-core single-chamber osmotic pump sustained-release preparations of an insoluble drug, this method may further comprise the steps:
1) insoluble drug is dissolved in the organic solvent, the weight ratio of described organic solvent and insoluble drug is 5: 1 to 20: 1; Described insoluble drug is felodipine or glipizide; Described organic solvent is selected from one or more in methanol, ethanol, isopropyl alcohol, acetone, chloroform or the carbon tetrachloride;
2) step 1) gained solution and low molecular saccharides penetrating agent are fully mixed, in 40-60 ℃ of drying, grind resulting mixture then, the low molecular saccharides mixture of medicine that obtained load; Described low molecular saccharides penetrating agent is selected from one or more in lactose, sucrose, fructose, glucose or the mannitol;
3) with step 2) the low molecular saccharides mixture of gained with help suspensoid, extender and other adjuvants to mix after, be prepared into single-tablet-core single-chamber osmotic pump sustained-release preparations according to conventional method; It is described that to help the weight ratio of suspensoid and insoluble medicine be 2: 1 to 10: 1; The weight ratio of extender and insoluble drug is 1: 10 to 1: 1; The weight ratio of low molecular saccharides penetrating agent and insoluble drug is 5: 1 to 50: 1.
2. method according to claim 1 is characterized in that the extender described in the step 3) is selected from one or more in poly(ethylene oxide), arabic gum, sodium alginate or the pregelatinized starch.
3, method according to claim 2 is characterized in that, the suspensoid that helps described in the step 3) is selected from soluble starch, sodium carboxymethyl cellulose, hypromellose, dextrin, Polyethylene Glycol or the gelatin one or more.
4. method according to claim 3 is characterized in that, the weight ratio of organic solvent described in the step 1) and insoluble drug is 10: 1.
5. method according to claim 4 is characterized in that step 2) in grind resulting mixture and cross 100 mesh sieves.
6. method according to claim 5 is characterized in that step 2) described in low molecular saccharides penetrating agent and the weight ratio of insoluble drug be 10: 1 to 25: 1; The weight ratio that helps suspensoid and insoluble medicine described in the step 3) is 5: 1, and the weight ratio of described extender and insoluble drug is 1: 5.
7. according to each described method among the claim 1-6, it is characterized in that, in described step 1), adopt one or more following measures to promote the dissolving of insoluble drug: to add 5 times surfactant, heating or supersound process being no more than drug weight; Described surfactant is selected from one or more in polyvinylpyrrolidone, polyethylene glycols, Tween 80, castor oil hydrogenated, sodium lauryl sulphate or the Stepanol MG.
8. single-tablet-core single-chamber osmotic pump sustained-release preparations according to the insoluble drug of each described method preparation among the claim 1-7.
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940578B (en) * | 2010-08-25 | 2012-07-25 | 山东新华制药股份有限公司 | Medicament composition for curing type 2 diabetes and preparation method thereof |
| CN102133205B (en) * | 2011-03-17 | 2013-12-11 | 山东新华制药股份有限公司 | Preparation method of glipizide osmotic pump controlled release tablet |
| CN102302469B (en) * | 2011-07-13 | 2016-01-06 | 合肥华方医药科技有限公司 | The preparation method of double layer osmotic pump controlled release felodipine sheet |
| CN104857515B (en) * | 2014-02-25 | 2020-01-10 | 中国科学院上海药物研究所 | Drug core composition for controlled release drug delivery and osmotic pump preparation containing the same |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5736159A (en) * | 1995-04-28 | 1998-04-07 | Andrx Pharmaceuticals, Inc. | Controlled release formulation for water insoluble drugs in which a passageway is formed in situ |
| US6814979B2 (en) * | 1996-10-25 | 2004-11-09 | Shire Laboratories, Inc. | Osmotic drug delivery system |
| CN1552323A (en) * | 2003-12-19 | 2004-12-08 | 沈阳药科大学 | Monolayer osmotic pump controlled releasing tablets of nimodipine |
| CN1640400A (en) * | 2004-01-08 | 2005-07-20 | 曹德英 | Felodipine controlled-release preparation |
| CN1692902A (en) * | 2004-11-12 | 2005-11-09 | 普尔药物科技开发（深圳）有限公司 | Colchicine osmosis pump tablet, and its prepn. method |
-
2006
- 2006-02-27 CN CNB2006100577809A patent/CN100350909C/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5736159A (en) * | 1995-04-28 | 1998-04-07 | Andrx Pharmaceuticals, Inc. | Controlled release formulation for water insoluble drugs in which a passageway is formed in situ |
| US6814979B2 (en) * | 1996-10-25 | 2004-11-09 | Shire Laboratories, Inc. | Osmotic drug delivery system |
| CN1552323A (en) * | 2003-12-19 | 2004-12-08 | 沈阳药科大学 | Monolayer osmotic pump controlled releasing tablets of nimodipine |
| CN1640400A (en) * | 2004-01-08 | 2005-07-20 | 曹德英 | Felodipine controlled-release preparation |
| CN1692902A (en) * | 2004-11-12 | 2005-11-09 | 普尔药物科技开发（深圳）有限公司 | Colchicine osmosis pump tablet, and its prepn. method |
Non-Patent Citations (4)
| Title |
|---|
| 口服渗透泵制剂的研究进展 陈志鹏.国外医学药学分册，第32卷第2期 2005 * |
| 药物新剂型与新技术 陆彬，436.448，人民卫生出版社 2005 * |
| 难溶性药物口服渗透泵片工艺的研究进展 卢恩先，江志强.药学学报，第36卷第3期 2001 * |
| 难溶性药物盐酸尼卡地平单室单层渗透泵片的制备 丁雪鹰等.中国药学杂志，第40卷第4期 2005 * |
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