CN101869554A - Doxazosin mesylate controlled release tablet and preparation technology thereof - Google Patents
Doxazosin mesylate controlled release tablet and preparation technology thereof Download PDFInfo
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- CN101869554A CN101869554A CN200910130966A CN200910130966A CN101869554A CN 101869554 A CN101869554 A CN 101869554A CN 200910130966 A CN200910130966 A CN 200910130966A CN 200910130966 A CN200910130966 A CN 200910130966A CN 101869554 A CN101869554 A CN 101869554A
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Abstract
The invention provides a doxazosin mesylate bi-layer osmotic pump controlled release tablet. The preparation contains doxazosin mesylate and polymer which is acceptable in pharmacy. The modified dosage form is the osmotic pump preparation which has the characteristic of zero order release when released in vivo, the release is stable, the preparation is also characterized by low frequency of use, convenient taking way, long lasting and stable curative effect, and the preparation solves the problems that in the current domestic market, the release of the doxazosin mesylate preparation is not stable and the frequency of use is high. The preparation of the invention comprises the following components by weight percent: 1-15% of doxazosin mesylate, 30-65% of auxiliary material controlling release in a boosting layer, 15-55% of auxiliary material controlling release in the boosting layer and the balance other auxiliary materials. The auxiliary materials controlling release in a drug layer can be polyoxyethylene, sodium chloride, hydroxypropyl methylcellulose and the like; the auxiliary materials controlling release in the boosting layer can be polyoxyethylene, hydroxypropyl methylcellulose, ethyl cellulose and the like; and membrane materials controlling release can be acetyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol and the like. The controlled release preparation of the invention can be used to cure diseases such as hypertension and prostatic hypertrophy in clinic.
Description
Technical field
The present invention relates to doxazosin-mesylate controlled-releasing preparation preparation, be specifically related to double-deck label two-chamber osmotic pump controlled-release tablet of a kind of oral Carclura and preparation method thereof.
Background technology
Carclura (Doxazosin Mesylate is abbreviated as DOX) is a kind of selectivity α
1Receptor blocking agent is mainly used in treatment essential hypertension and optimum prostatitis hypertrophy.Compare with similar medicine, therefore characteristics such as hypotensive effect is strong, toxicity is little, better tolerance that it has are hypertension first-line treatment medicine, also are that a kind of clinical efficacy of treatment prostatic hyperplasia is affirmed, use more medicine.This product is by the research and development of Pfizer (Pfizer) company, and homemade DOX still was in the research in Denmark's Initial Public Offering in 1988.
Cardiovascular disease is the No.1 killer who threatens human health, and much more hypertension be one of diseases of wherein seeing, China hyperpietic increases year by year in recent years, at present prevalence about 12%.Prostatic hyperplasia (BPH) is commonly encountered diseases, the frequently-occurring disease of elderly men.Male more than 50 years old has 40% people that in various degree prostatic hyperplasia is arranged more.According to statistics, in the elderly men about 80 years old, the sickness rate of BPH is up to 90%.The age of onset of China's prostatosis constantly is tending towards rejuvenation in recent years.Therefore no matter be hypertension or prostatic hyperplasia, all need really effectively medicine badly.Doxazosin is as α
1Adrenergic receptor blocker has less side effect than alpha blocker in the past, therefore has the potentiality that increase patient tolerability, can not only be by retardance α
1Receptor and the effect that reaches blood vessel dilating, reduce resistance, bring high blood pressure down, and can be by the alpha adrenergic receptor of selective exclusion prostate smooth muscle substrate, tunicle and neck of bladder, cause that this position is smoothly lax, resistance reduces, and then reaches the effect of blocking symptom that improves BPH.
Pfizer improves original conventional tablet, adopt Alza company osmotic pump controlled-releasing technology (also to claim gastrointestinal therapeutic system, GITS), developed the durative action preparation " can how magnificent " (Cardura XR) of this kind, sick successively in the listing of ground such as Europe, China and the U.S..Its unique controlled-release technology has improved the pharmacokinetic characteristics of " can how magnificent " ordinary tablet, has further reduced the side effect of conventional tablet, takes into account curative effect and safety, for the outgrowth Drug therapy of hypertension and prostatitis provides a new selection.
Because Carclura is slightly soluble in water (25 ℃ time dissolubility be 0.8%), in the microenvironment of label, be difficult to form higher concentration and osmotic pressure is kept effective rate of releasing drug, so need to adopt double layer osmotic pump preparation technique (being called PPOP or push-pull type osmotic pumps), make medicine and medicated layer macromolecule release drug release hole with suspension form boosting floor height peak.The controlled release preparation of " can how magnificent " has promptly adopted this technology.This technology is that present insoluble drug is made the osmotic pump type preparation way of maturation, optimum suitability for industrialized production the most.But this technical difficulty is big, the production technology relative complex, and present domestic many enterprises are developing doxazosin, but mostly are conventional tablet and capsule, and the research and development of controlled releasing penetrant pump are less relatively.
Summary of the invention
The invention provides a kind of preparation method of Carclura double layer osmotic pump type controlled release tablet, have that convenient drug administration, effect are lasting, a stable curative effect, characteristics that toxic and side effects is little.
Preparation of the present invention contains following component by weight percentage:
Carclura 1-15%
Play the adjuvant 30-65% of controlled release effect in the medicated layer
Play the adjuvant 15-55% of controlled release effect in the boosting layer
Other adjuvant surpluses
This preparation is for being the double-layer osmotic pump controlled-release tablet of major impetus with the osmotic pressure.
The above-mentioned adjuvant that plays the controlled release effect is: the adjuvant that plays the controlled release effect in the medicated layer can be selected from polyoxyethylene, sodium chloride, hypromellose, ethyl cellulose, lactose, mannitol, fructose, glucose, sucrose, sodium hydrogen phosphate.The adjuvant that plays the controlled release effect in the boosting layer can be selected from polyoxyethylene, hypromellose, ethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crosslinked polyethylene pyrrole lattice alkane ketone, carbopol, sodium chloride.
The membrane material of its controlled-release function can be selected from cellulose acetate, ethyl cellulose, hypromellose, polyethylene, polyethylene glycols.
Above-mentioned adjuvant is pharmaceutical carrier, expanding material, permeation-promoter, porogen, binding agent, lubricant, antiplastering aid, semipermeable membrane material, plasticizer, lucifuge agent, coloring agent, solvent.Pharmaceutical carrier, expanding material can adopt polyoxyethylene, ethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crosslinked polyethylene pyrrole lattice alkane ketone, carbopol etc.; Permeation-promoter can adopt sodium chloride, lactose, mannitol, fructose, glucose, sucrose etc.; Binding agent can adopt polyethylene pyrrole lattice alkane ketone, hydroxypropyl cellulose etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Coloring agent can adopt iron oxide red, iron oxide yellow etc.; Porogen can adopt sucrose, mannitol, Polyethylene Glycol (Macrogol 200-400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000); Plasticizer can adopt Methyl Benzene-o-dicarboxylate, ethyl phthalate, triethyl citrate, Polyethylene Glycol; Opacifier can adopt titanium dioxide, Pulvis Talci, silicon dioxide etc.; Membrane material can adopt cellulose acetate, polyethylene, ethyl cellulose etc.; Solvent can adopt acetone, dehydrated alcohol, ethanol, water etc.
The drug release hole of coated tablet on the medicated layer surface is laser boring or mechanical punching, and the aperture is the 0.2-1.0 millimeter.
The dosage form of above-mentioned preparation has double-layer tablet type, coating type or other dosage forms.
Advantage of the present invention is: medicining times is few, taking convenience, blood drug level floating are little, and drug action is lasting, stable curative effect, and toxic and side effects is little.
Description of drawings:
The cumulative release curve of the preparation of the present invention of Fig. 1 embodiment 1 preparation China with how
The specific embodiment
Below in conjunction with specific embodiment and relevant drawings, the present invention is carried out detailed explanation, still, below the embodiment that provided just for the present invention is described, be not limitation of the present invention.
Embodiment 1:
Present embodiment 1 tablet that adopts the known method of pharmaceuticals industry to make contains following composition by weight percentage:
Medicated layer:
Carclura 2.8%
Polyoxyethylene (molecular weight 200,000) 50.5%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The boosting layer:
Polyoxyethylene (molecular weight 7,000,000) 28.1%
Hydroxypropyl cellulose 1.4%
Sodium chloride 10.1%
PVP(K30) 2.8％
Iron oxide red 0.3%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The semipermeable membrane coating solution is formed:
Cellulose acetate 98.0%
Macrogol 4000 2.0%
Acetone: water (95: 5) 5.0% (w/v)
Moistureproof coating liquid is formed:
Hypromellose 42.9%
1,2-propylene glycol 2.0% (v/v)
Pulvis Talci 28.6%
Titanium dioxide 28.6%
Ethanol: water 7.0% (w/v)
Adopt film-coated technique, Carclura is made double-layer osmotic pump controlled-release tablet, medicated layer is carried out laser or mechanical punching, the aperture is: the 0.2-1.0 millimeter reaches the purpose of controlled release.
Embodiment 2:
Present embodiment 2 tablets that adopt the known method of pharmaceuticals industry to make contain following composition by weight percentage:
Medicated layer:
Carclura 2.6%
Polyoxyethylene (molecular weight 200,000) 43.5%
Sodium chloride 11.2%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The boosting layer:
Polyoxyethylene (molecular weight 7,000,000) 26.6%
Sodium chloride 12.6%
PVP(K30) 2.8％
Iron oxide red 0.3%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The semipermeable membrane coating solution is formed:
Cellulose acetate 91.2%
Triethyl citrate 6.4%
PEG400 2.4%
Acetone: water (95: 5) 3.6% (w/v)
Moistureproof coating liquid is formed:
Hypromellose 42.9%
1,2-propylene glycol 2.0% (v/v)
Pulvis Talci 28.6%
Titanium dioxide 28.6%
Ethanol: water 7.0% (w/v)
Adopt film-coated technique, Carclura is made double-layer osmotic pump controlled-release tablet, medicated layer is carried out laser or mechanical punching, the aperture is: the 0.2-1.0 millimeter reaches the purpose of controlled release.
Embodiment 3:
Medicated layer:
Carclura 2.8%
Carbopol 41.3%
Lactose 14.2%
Pulvis Talci 0.2%
The boosting layer:
Polyoxyethylene (molecular weight 6,000,000) 29.1%
Lactose 11.9%
Pulvis Talci 0.2%
Iron oxide red 0.3%
10%PVP ethanol liquid is an amount of
The semipermeable membrane coating solution is formed:
Cellulose acetate 80.6%
Ethyl cellulose 9.6%
Methyl Benzene-o-dicarboxylate 9.8%
Acetone: water (95: 5) 3.5% (w/v)
Moistureproof coating liquid is formed:
Hypromellose 42.9%
1,2-propylene glycol 2.0% (v/v)
Pulvis Talci 28.6%
Titanium dioxide 28.6%
Ethanol: water 7.0% (w/v)
Adopt film-coated technique, Carclura is made double-layer osmotic pump controlled-release tablet, medicated layer is carried out laser or mechanical punching, the aperture is: the 0.2-1.0 millimeter reaches the purpose of controlled release.
Embodiment 4:
Present embodiment 4 tablets that adopt the known method of pharmaceuticals industry to make contain following composition by weight percentage:
Medicated layer:
Carclura 2.8%
Polyoxyethylene (molecular weight 200,000) 50.5%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The boosting layer:
Carboxymethyl starch sodium 32.9%
Sodium chloride 13.1%
Iron oxide red 0.3%
Magnesium stearate 0.2%
10%PVP ethanol liquid is an amount of
The semipermeable membrane coating solution is formed:
Cellulose acetate 91.3%
Triethyl citrate 6.3%
Polyethylene glycol 1500 2.4%
Acetone: water (95: 5) 3.6% (w/v)
Moistureproof coating liquid is formed:
Hypromellose 42.9%
1,2-propylene glycol 2.0% (v/v)
Pulvis Talci 28.6%
Titanium dioxide 28.6%
Ethanol: water 7.0% (w/v)
Adopt film-coated technique, Carclura is made double-layer osmotic pump controlled-release tablet, medicated layer is carried out laser or mechanical punching, the aperture is: the 0.2-1.0 millimeter reaches the purpose of controlled release.
Embodiment 5:
Drug release determination
Laboratory sample: doxazosin-mesylate controlled-releasing tablet of the present invention, according to the embodiment of the invention 1 preparation; " can how magnificent " be bought from market.
Release medium: 0.1mol/L hydrochloric acid solution
Drug release determination method: according to release (two appendix XD first methods of Chinese Pharmacopoeia version in 2005) algoscopy, adopt dissolution method second subtraction unit, rotating speed is 75 rev/mins, measure the cumulative release amount of Carclura, and with how China (the Pfizer production of preparation of the present invention and listing, the packing of Dalian Pfizer) measurement result compares, and the result as shown in Figure 1.
Experimental result: referring to Fig. 1 as can be known, the release of doxazosin-mesylate controlled-releasing tablet of the present invention and " can how magnificent " is consistent substantially.
Claims (7)
1. Carclura double-layer osmotic pump controlled-release tablet, it comprises medicated layer and boosting layer, said preparation contains following composition by weight percentage:
Carclura 1-15%
Play the adjuvant 30-65% of controlled release effect in the medicated layer
Play the adjuvant 15-55% of controlled release effect in the boosting layer
Other adjuvant surpluses
2. Carclura double-layer osmotic pump controlled-release tablet according to claim 1 is characterized in that: the adjuvant that plays the controlled release effect in the medicated layer can be selected from polyoxyethylene, sodium chloride, hypromellose, ethyl cellulose, lactose, mannitol, fructose, glucose, sucrose, sodium hydrogen phosphate.
3. Carclura double-layer osmotic pump controlled-release tablet according to claim 1, it is characterized in that: the adjuvant that plays the controlled release effect in the boosting layer can be selected from polyoxyethylene, hypromellose, ethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crosslinked polyethylene pyrrole lattice alkane ketone, carbopol, sodium chloride.The membrane material of its controlled-release function can be selected from cellulose acetate, ethyl cellulose, hypromellose, polyethylene, polyethylene glycols.
4. Carclura double-layer osmotic pump controlled-release tablet according to claim 1 is characterized in that: adjuvant is pharmaceutical carrier, expanding material, permeation-promoter, porogen, binding agent, lubricant, antiplastering aid, semipermeable membrane material, plasticizer, lucifuge agent, coloring agent, solvent.
5. Carclura double-layer osmotic pump controlled-release tablet according to claim 1 is characterized in that: the drug release hole of coated tablet on the medicated layer surface is laser boring or mechanical punching, and the aperture is the 0.2-1.0 millimeter.
6. Carclura double-layer osmotic pump controlled-release tablet according to claim 1 is characterized in that: label is the double-deck label that comprises medicated layer and boosting layer.
7. according to claim 1 or 2 or 3 or 4 or 5 described Carclura double-layer osmotic pump controlled-release tablets, it is characterized in that: the dosage form of preparation is for being the osmotic pump controlled release tablet of major impetus with the osmotic pressure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910130966A CN101869554A (en) | 2009-04-21 | 2009-04-21 | Doxazosin mesylate controlled release tablet and preparation technology thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910130966A CN101869554A (en) | 2009-04-21 | 2009-04-21 | Doxazosin mesylate controlled release tablet and preparation technology thereof |
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| CN101869554A true CN101869554A (en) | 2010-10-27 |
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| CN200910130966A Pending CN101869554A (en) | 2009-04-21 | 2009-04-21 | Doxazosin mesylate controlled release tablet and preparation technology thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111388439A (en) * | 2020-03-16 | 2020-07-10 | 乐普制药科技有限公司 | Quick-release and slow-release tablet containing doxazosin mesylate and preparation method thereof |
| CN115350160A (en) * | 2022-10-20 | 2022-11-18 | 华润双鹤利民药业（济南）有限公司 | Paliperidone sustained-release preparation and preparation method thereof |
-
2009
- 2009-04-21 CN CN200910130966A patent/CN101869554A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111388439A (en) * | 2020-03-16 | 2020-07-10 | 乐普制药科技有限公司 | Quick-release and slow-release tablet containing doxazosin mesylate and preparation method thereof |
| CN111388439B (en) * | 2020-03-16 | 2022-04-26 | 乐普制药科技有限公司 | Quick-release and slow-release tablet containing doxazosin mesylate and preparation method thereof |
| CN115350160A (en) * | 2022-10-20 | 2022-11-18 | 华润双鹤利民药业（济南）有限公司 | Paliperidone sustained-release preparation and preparation method thereof |
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Application publication date: 20101027 |