CN102058555A - Doxazosin controlled release tablet - Google Patents
Doxazosin controlled release tablet Download PDFInfo
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- CN102058555A CN102058555A CN2011100066503A CN201110006650A CN102058555A CN 102058555 A CN102058555 A CN 102058555A CN 2011100066503 A CN2011100066503 A CN 2011100066503A CN 201110006650 A CN201110006650 A CN 201110006650A CN 102058555 A CN102058555 A CN 102058555A
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- doxazosin
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Abstract
The invention relates to a doxazosin controlled release tablet composition which contains effective quantities of doxazosin and polyoxyethylene and selectively comprises one or more pharmaceutically acceptable auxiliary materials. The invention also relates to a doxazosin controlled release tablet which comprises a single layer of tablet core and a coating film wrapped on the tablet core, medicine release holes are arranged at one side of the tablet, the tablet core comprises effective quantities of doxazosin and polyoxyethylene and selectively comprises one or more pharmaceutically acceptable auxiliary materials, and the coating film is a semi-transparent film.
Description
Technical field
The present invention relates to drug preparation technique.More specifically, the present invention relates to a kind of doxazosin controlled release tablet compositions, a kind of doxazosin controlled release tablet and their preparation method.
Background of invention
Doxazosin (Doxazosin) belongs to α 1 blocker, can cause the lax and expansion of blood vessel (comprising vein and tremulous pulse), and blood flow increasing also can make prostate and neck of bladder loosening all muscles, promotes to urinate.This medicine is used for the treatment of hypertension and and benign prostatic hyperplasia clinically.Its mesylate commonly used clinically, i.e. Carclura, chemical name is 1-(4-amino-6,7-dimethoxy-2-quinazolyl)-4-[(2,3-dioxy-1,4-benzo two evil-2-yls) carbonyl] piperazine methanesulfonate, structural formula is as follows:
The pharmacological action of doxazosin mainly shows: (1) blood pressure lowering: selectively acting makes peripheral vasodilation in joint back α 1-adrenoceptor, and peripheral vascular resistance reduces and brings high blood pressure down.(2) diastole smooth muscle: in the α 1--of prostate and neck of bladder smooth muscle adrenoceptor, make neck of bladder, prostate, capsula prostatica smooth muscle loosening, urethra and bladder resistance lower, thereby alleviate the urethral obstruction symptom that prostatic hyperplasia causes.(3) blood fat reducing: slight hypercholesterolemia reducing (2-3%), LDL-cholesterol (4%), and the HDL-cholesterol (4%) that slightly raises.
Carclura is white or off-white color crystalline powder, and odorless is tasteless.This product is slightly soluble in ethanol, methanol, soluble,very slightly in water (dissolubility is about 0.8%, 25 ℃).Because Carclura is extremely low at dissolubility, is difficult to be prepared into general sustained-release preparation.
Sustained-release preparation has been compared lot of superiority with ordinary preparation, and for example, sustained-release preparation can be kept the required blood drug level of treatment the long period, and the peak valley that reduces blood drug level simultaneously changes, and reduces the incidence rate and the order of severity of toxic and side effects.Sustained-release preparation can also be taken number of times by minimizing, improves patient's compliance.Prostatosis patient and hyperpietic need take medicine for a long time usually and control blood level, and in this case, the superiority of sustained-release preparation is more obvious.Therefore the doxazosin controlled release tablet is significant to prostatosis and hypertensive clinical treatment, has widespread demand in associated patient.
Pfizer Inc. produce how China (Cardura XL) is the double-layer osmotic pump controlled-release tablet of doxazosin, its preparation principle and technology and Chinese patent application 200710177989.3 basically identicals, what adopt the preparation of this principle and method is single chamber double-layer osmotic pump tablet (push-pull osmotic pump sheet).Be that one deck is a medicine layer, by medicine add some hydrotropies, suspending agent is formed; Another layer is the boosting layer, mainly by forming (specific explanations sees below) by swollen macromolecule after the suction.This single chamber double-layer osmotic pump controlled-release tablet complicated process of preparation.Chinese patent application 200710165689.3, by use necessary solubilizing agent in the heart at sheet, the salify type of solubilizing agent or change doxazosin, it perhaps is surfactant, all increased the dissolubility of doxazosin, thereby applied for a kind of doxazosin controlled release tablet preparation method of single chamber monolayer, its inventive principle and Chinese patent application 200810103429.8 (a kind of Gliclazide controlled release tablets) have similar part, but its technology is more complicated, requirement is all punched at the upper and lower surface of tablet, acquires a certain degree of difficulty in industrialization.
The invention provides and be different from a kind of doxazosin controlled release tablet compositions of prior art, a kind of doxazosin controlled release tablet, and their preparation method, more simple and easy, as to be convenient to industrialization production.
Summary of the invention
1, one of purpose of the present invention provides a kind of doxazosin controlled release tablet compositions, and it contains the doxazosin and the polyoxyethylene of effective dose, and optionally contains one or more acceptable accessories.
2, another object of the present invention has provided a kind of doxazosin controlled release tablet, comprise the single-layer sheet heart and be wrapped in sheet coating membrane in the heart, and drug release hole is arranged in tablet one side, wherein the sheet heart contains the doxazosin and the polyoxyethylene of effective dose, and optionally containing one or more acceptable accessories, coating membrane is a semipermeable membrane.
3, a further object of the present invention has provided the preparation method of doxazosin controlled release tablet.
Detailed Description Of The Invention
Doxazosin controlled release tablet of the present invention is the osmotic pump type controlled release tablet of single chamber monolayer single face punching.
Controlled releasing penetrant pump is as the typical case of controlled release preparation representative, and it is obvious to have the zero-order release feature, and drug release behavior is not subjected to the influence of factors such as media environment pH value, gastrointestinal peristalsis and food, and characteristics such as release dependency in inside and outside is good.Osmotic pump tablet mainly contains single chamber and two chambers two big classes.Wherein, two-chamber osmotic pump sheet preparation technology is comparatively complicated, at present product-free listing temporarily; The single chamber osmotic tablets can be divided into monolayer and double-layer osmotic pump tablet again, both at home and abroad all existing procucts listings.
Osmotic pump tablet is to have utilized the osmotic pressure principle.Enter the intracardiac moisture of sheet by semipermeable membrane, make sheet medicine and osmotic pressure active substance (being boosting layer material in the double-layer tablet) dissolving and swelling in the heart, produce the very medicine saturated solution of hyperosmosis of tool.And because coating membrane be the relative stiffness structure, along with moisture continue enter, produce a higher hydrostatic pressing in the heart at sheet, the saturated solution of force medication continues to disengage with constant rate of speed from small delivery aperture.Its emission is suitable with the water yield of advancing in people's film, and molten most up to medicine, when solution was no longer saturated, rate of releasing drug just reduced gradually.
What optimum was made osmotic pump tablet is the medicine with moderate solubility (50～300g/L water).After moisture enters the sheet heart, can form rapidly and have the two fun gi polysaccharides saturated solution, thereby guarantee certain rate of releasing drug, produce therapeutic effect.Though and insoluble drug can form saturated solution. its medicine saturated concentration value is less, and rate of release is also just very little, does not reach effective blood drug concentration, and the very difficult release of medicine is fully, and when Swertia Tablet was discharged by human body, sheet still had high amount of drug to exist in the heart.Therefore, to improve its dissolubility to insoluble drug and promote release, just can prepare good penetration pump preparation.
Insoluble drug medicine saturated concentration is extremely low, is difficult to reach effective treatment concentration, it is discharged need a large amount of osmotic pressure active substances fully, weighs scope in theory even above normal sheet.So for insoluble drug, suitable is single chamber double-layer osmotic pump tablet (push-pull osmotic pump sheet).Be that one deck is a medicine layer, by medicine add some hydrotropies, suspending agent is formed; Another layer is the boosting layer, mainly by forming by swollen macromolecule after the suction.After taking medicine, moisture enters the sheet heart by semipermeable membrane, makes medicine dissolution and suspendible at medicine layer, makes the macromolecule swelling at the boosting layer, produces a motive force, the suspension of medicine is released by small delivery aperture with given pace, thereby reached the purpose of constant speed release medicine.Its advantage is that the zero level feature is obvious, release is complete, solved the release problem of insoluble drug well, but its shortcoming is the technical merit of technology has relatively high expectations, comprise double-layer tablet compacting, when punching levels identification etc., this has limited its application to a certain extent.
Research worker of the present invention is on the basis of a large amount of tests, be surprised to find and adopt suitable polyoxyethylene to be prepared into the osmotic pump controlled release tablet of doxazosin single chamber monolayer single face punching as osmotic pressure active matter mass-energy, solved doxazosin is difficult to prepare the mono-layer osmotic pump sheet as the slightly solubility medicine a difficult problem, realized the controlled-release effect that needs double-layer osmotic pump tablet just can reach usually by relative simple technology, and by dog body giving drugs into nose dynamic test show with sell in the market how China (Cardura XL) has data in the identical body.
The invention provides a kind of doxazosin controlled release tablet compositions, it contains the doxazosin of effective dose and as the polyoxyethylene of osmotic pressure active substance, and optionally contains one or more acceptable accessories.
Polyoxyethylene (Polyethylene oxide) is-(OCH
2CH
2)-
nNonionic homopolymer, wherein n represents the average number of oxygen ethyl, usually between 2,000 to about 100,000.It is a water-soluble resin, and molecular weight generally about 100,000 to about 7,000, between 000, has different viscositys in the aqueous solution that do not coexist according to molecular weight.Business-like polyoxyethylene often is divided into different model according to the difference of mean molecule quantity.For example, the POLYOX of Dow chemical company
TMIn the series of products, the molecular weight of WSR N-10NF is about 100,000, the molecular weight of WSR N-80NF is about 200,000, and the molecular weight of WSR N-750NF is about 300,000, the molecular weight of WSR-205NF is about 600,000, the molecular weight of WSR-1105NF is about 900,000, and the molecular weight of WSR N-12K NF is about 1,000,000, the molecular weight of WSR N-60KNF is about 2,000,000, the molecular weight of WSR-301NF is about 4,000,000, the molecular weight of WSRCoagulant NF is about 5,000,000, the molecular weight of WSR-303NF is about 7,000,000.
Polyoxyethylene is selected from molecular weight 100,000～7 among the present invention, one or more in 000,000, preferred molecular weight 100,000～300,000 and molecular weight 4,000,000～7,000, in 000 one or more, more preferably molecular weight is respectively 20,000 and 7,000, two kinds of polyoxyethylene of 000.
Polyoxyethylated consumption decides according to polyoxyethylated molecular weight of adopt and the controlled-release effect that expection reaches among the present invention, and amount ranges generally accounts for 27%～46% of tablet weight, preferably accounts for 36%～46% of tablet weight.
Part embodiment of the present invention has been used molecular weight 20,000 and 7,000 simultaneously, two kinds of polyoxyethylene of 000.Molecular weight 20,000 polyoxyethylene account for 19%～29% of tablet weight, molecular weight 7,000, and 000 polyoxyethylene accounts for 8%～23% of tablet weight.
Polyoxyethylene among the present invention can also be the form of share with the active macromolecular material of other osmotic pressuries.The active macromolecular material of other osmotic pressuries comprises hypromellose, arabic gum, polyvidone, sodium alginate etc.
One or more pharmacy acceptable auxiliary are selected from any pharmaceutic adjuvant that can be used for controlled release tablet, include but not limited to filler, penetrating agent, binding agent, lubricant, fluidizer etc.
Wherein filler and penetrating agent are selected from lactose, mannitol, sodium chloride etc., preferred lactose.
Wherein binding agent is selected from 30 POVIDONE K 30 BP/USP 30, pregelatinized Starch, starch slurry, low-molecular-weight hypromellose etc., preferred 30 POVIDONE K 30 BP/USP 30.
Wherein lubricant is selected from magnesium stearate, stearic acid, stearyl alcohol etc., preferred magnesium stearate.
Wherein fluidizer is selected from gaseous state silicon dioxide, Pulvis Talci etc., preferred gaseous state silicon dioxide.
Doxazosin controlled release tablet compositions of the present invention can be used for hypertension and benign prostate disease, be prepared into the doxazosin controlled release tablet after, it is stable to have a drug release rate, drug release rate is not influenced by gastrointestinal tract environment, the characteristics that patient's compliance is high.
The invention provides a kind of doxazosin controlled release tablet, comprise the single-layer sheet heart and be wrapped in sheet coating membrane in the heart, and drug release hole is arranged in tablet one side.The sheet heart contains the doxazosin and the polyoxyethylene of effective dose, and optionally contains one or more acceptable accessories.Coating membrane is a semipermeable membrane.
Sheet polyoxyethylene in the heart is selected from molecular weight 100,000～7, one or more in 000,000, preferred molecular weight 100,000～300,000 and molecular weight 4,000,000～7,000, in 000 one or more, more preferably molecular weight is respectively 20,000 and 7,000, two kinds of polyoxyethylene of 000.
Polyoxyethylated consumption is according to the polyoxyethylated molecular weight of adopt and expect that the controlled-release effect that reaches decides, and amount ranges generally accounts for 27%～46% of tablet weight, preferably accounts for 36%～46% of tablet weight.
Molecular weight 20,000 and 7,000 have been used simultaneously in the part embodiment of the present invention, two kinds of polyoxyethylene of 000.Molecular weight 20,000 polyoxyethylene account for 19%～29% of tablet weight, molecular weight 7,000, and 000 polyoxyethylene accounts for 8%～23% of tablet weight.
Sheet polyoxyethylene in the heart can also be the form of share with the active macromolecular material of other osmotic pressuries.The active macromolecular material of other osmotic pressuries comprises hypromellose, arabic gum, polyvidone, sodium alginate etc.
One or more pharmacy acceptable auxiliary can be selected from any pharmaceutic adjuvant that can be used for sustained-release preparation, include but not limited to filler, penetrating agent, binding agent, lubricant, fluidizer etc.
Wherein filler and penetrating agent are selected from lactose, mannitol, sodium chloride etc., preferred lactose.
Wherein binding agent is selected from 30 POVIDONE K 30 BP/USP 30, pregelatinized Starch, starch slurry, low-molecular-weight hypromellose etc., preferred 30 POVIDONE K 30 BP/USP 30.
Wherein lubricant is selected from magnesium stearate, stearic acid, stearyl alcohol etc., preferred magnesium stearate.
Wherein fluidizer is selected from gaseous state silicon dioxide, Pulvis Talci etc., preferred gaseous state silicon dioxide.
Preferred sheet contains filler, penetrating agent, binding agent and solubilizing agent in the heart.
Coating membrane is a semipermeable membrane in the doxazosin controlled release tablet of the present invention, mainly contains the coating filmogen.The coating filmogen mostly is to have semipermeability and medicine not to be had chemosmotic macromolecular material liquid such as water.Be to increase the pliability of coating membrane, prevent that medicine from leaking and make the corrosion of tablet own, and guarantee inside and outside the tablet big osmotic pressure is arranged, can add plasticizer.If coating membrane adopts non-laser beam drilling, also need add porogen.
The coating filmogen is selected from cellulose acetate, acrylic resin, ethyl cellulose etc. among the present invention, preferred cellulose acetate.
Plasticizer is selected from triethyl citrate, Oleum Ricini, Tween 80, phthalic acid ester etc., optimization citric acid triethyl.
Porogen is selected from PEG400, Macrogol 600, cetomacrogol 1000 and polyethylene glycol 1500 etc., preferred polyethylene glycol 1500.
Doxazosin controlled release tablet of the present invention has a drug release hole on the surface of coating membrane.
The invention provides the preparation method of doxazosin controlled release tablet of the present invention.
Granulation behind the mixings such as doxazosin and polyoxyethylene, binding agent, filler, short penetrating agent, drying, coating behind the tablet forming heart at last in the one side punching of tablet, makes the doxazosin controlled release tablet.
Punching can adopt laser or mechanical mode to carry out.Early stage document reported with machine drilling once and prepared osmotic pump tablet that the big production of the inapplicable mechanization of this method only limited to laboratory and manufactures experimently in a small amount; Often adopt the mode of laser boring at present in the commercial production, this method is used the energy source of laser as pore, and is little to the damage of coating membrane, high efficiency; The drift that has also had bibliographical information to adopt to improve, the sheet before coating forms indenture in the heart, directly formation drug release hole behind the coating.
" effective dose " among the present invention in " doxazosin of effective dose " is meant the amount that can form effective treatment blood drug level behind the tablet in vivo of taking.
Doxazosin controlled release tablet of the present invention belongs to the slow-release tablet agent.Because controlled release tablet and slow releasing tablet are difficult to distinguish sometimes, though doxazosin controlled release tablet of the present invention release more approaches zero order kinetics, also may be called as the doxazosin slow releasing tablet, doxazosin slow releasing tablet in such cases still belongs within the scope of the invention.
By the release result of the test as seen, adopt the doxazosin controlled release tablet of the present invention's preparation, in 0～16 hour, can keep the characteristics of good constant release medicine.And drug release rate can reach the purpose of clinical treatment, can be used for hypertension and benign prostate treatment of diseases.Embodiment 3 doxazosin controlled release tablet and Pfizer Inc. produce how China's (Cardura XL) release profiles in the release medium of United States pharmacopoeia specifications shows that both releases are for very similar, release in vitro zero level trend is obvious.How China's (Cardura XL) single dose and multiple dose that embodiment 3 doxazosin controlled release tablet and Pfizer Inc. produce all have bioequivalence in the test of Beagle dog interior medicine dynamics.
Description of drawings
Fig. 1 is how China's (Cardura XL) release profiles in the release medium of United States pharmacopoeia specifications that embodiment 3 doxazosin controlled release tablet and Pfizer Inc. produce.
Fig. 2 is how China's (Cardura XL) blood drug level-time graph in the single dose of drug dynamic test in Beagle dog body that embodiment 3 doxazosin controlled release tablet and Pfizer Inc. produce.
Fig. 3 is how China's (Cardura XL) blood drug level-time graph in the multiple dose pharmacokinetics test in Beagle dog body that embodiment 3 doxazosin controlled release tablet and Pfizer Inc. produce.
The specific embodiment
Following embodiment further introduces and sets forth the present invention, but does not limit the present invention in any way.
Polyoxyethylene 303 refers to the POLYOX WSR-303NF of Dow chemical company among the embodiment, and molecular weight is about 7,000,000; Polyoxyethylene N80 refers to that the molecular weight of the POLYOX WSR N-80NF of Dow chemical company is about 200,000.
Embodiment 1
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| Polyoxyethylene 303 | 25 |
| |
60 |
| Lactis Anhydrous | 120 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Sheet heart preparation method:
1, gets doxazosin and cross 80 mesh sieves;
2, take by weighing doxazosin, lactose and 1/2 recipe quantity polyoxyethylene N80 by recipe quantity, mix homogeneously adds 5% an amount of povidone solution system soft material, crosses 26 mesh sieves and granulates, and 40 ℃ of forced air dryings are complete;
3, with the polyoxyethylene N80 of surplus and recipe quantity polyoxyethylene 303, gaseous state silicon dioxide, magnesium stearate mix homogeneously;
4, treat particle drying back (pellet moisture is controlled in 2%) fully, 24 mesh sieve granulate, even with above-mentioned powder mixes, select the stamping of 7.5mm scrobicula.
Coating fluid prescription (1000ml coating solution consumption)
Cellulose acetate 26.7g
Polyethylene glycol 1500 4g
Triethyl citrate 2.3g
Acetone 900ml
Water 100ml
Compound method:
1, take by weighing the 4g polyethylene glycol 1500, add water 100ml, immersion makes it dissolving fully, gets solution A;
2, take by weighing the 26.7g cellulose acetate and add 900ml acetone, be stirred to dissolving fully, get solution B;
3, solution A is added in the solution B, treat solution clarification after, add the triethyl citrate of 2.3g, stir, promptly.
The coating operation:
Adopt film-coated routine operation mode to carry out the coating operation, reaching 6.0%～8.0% with the tablet coating weightening finish is optimal result, after coating finishes, solidifies 24 hours down in 40 ℃, promptly.
Punching:
Get the tablet behind the coating, adopt laser or mechanical system on the arbitrary face of tablet, to make a call to the aperture of a diameter 0.4～0.8mm, promptly get doxazosin controlled release tablet finished product.
Embodiment 2
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| Polyoxyethylene 303 | 20 |
| |
50 |
| Lactis Anhydrous | 120 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Prepare the sheet heart according to sheet heart recipe quantity according to the sheet heart preparation method of embodiment 1, adopt the coating solution identical, and use and embodiment 1 identical coating and drilling method prepares present embodiment doxazosin controlled release tablet finished product with embodiment 1.
Embodiment 3
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| Polyoxyethylene 303 | 40 |
| |
40 |
| Lactis Anhydrous | 90 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Prepare the sheet heart according to sheet heart recipe quantity according to the sheet heart preparation method of embodiment 1, adopt the coating solution identical, and use and embodiment 1 identical coating and drilling method prepares present embodiment doxazosin controlled release tablet finished product with embodiment 1
Embodiment 4
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| Polyoxyethylene 303 | 25 |
| |
60 |
| Sodium chloride | 220 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Sheet heart preparation method:
1, gets doxazosin and cross 80 mesh sieves;
2, take by weighing doxazosin, sodium chloride and 1/2 recipe quantity polyoxyethylene N80 by recipe quantity, mix homogeneously adds 5% an amount of povidone solution system soft material, crosses 26 mesh sieves and granulates, and 40 ℃ of forced air dryings are complete;
3, with the polyoxyethylene N80 and the recipe quantity polyoxyethylene 303 of surplus, gaseous state silicon dioxide, magnesium stearate mix homogeneously;
4, treat particle drying back (pellet moisture is controlled in 2%) fully, 24 mesh sieve granulate, even with above-mentioned powder mixes, select the stamping of 8mm scrobicula.
Adopt the coating solution identical, and use and embodiment 1 identical coating and drilling method prepares present embodiment doxazosin controlled release tablet finished product with embodiment 1
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| |
60 |
| Hypromellose (4000cp) | 25 |
| Lactis Anhydrous | 170 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Sheet heart preparation method:
1, gets doxazosin and cross 80 mesh sieves;
2, take by weighing doxazosin, lactose and 1/2 recipe quantity polyoxyethylene N80 by recipe quantity, mix homogeneously adds 5% an amount of povidone solution system soft material, crosses 26 mesh sieves and granulates, and 40 ℃ of forced air dryings are complete;
3, with the polyoxyethylene N80 of surplus and recipe quantity hypromellose K4M, gaseous state silicon dioxide, magnesium stearate mix homogeneously;
4, treat particle drying back (pellet moisture is controlled in 2%) fully, 24 mesh sieve granulate, even with above-mentioned powder mixes, select the stamping of 7.5mm scrobicula.
Adopt the coating solution identical, and use and embodiment 1 identical coating and drilling method prepares present embodiment doxazosin controlled release tablet finished product with embodiment 1
Embodiment 6
Sheet heart prescription:
| Component | Content mg/ sheet |
| Doxazosin | 4 |
| Polyoxyethylene 303 | 40 |
| |
40 |
| Mannitol | 90 |
| 5% polyvidone alcoholic solution | 0.01ml |
| Gaseous state silicon dioxide | 0.5 |
| Magnesium stearate | 0.5 |
Sheet heart preparation method:
1, gets doxazosin and cross 80 mesh sieves;
2, take by weighing doxazosin, mannitol and 1/2 recipe quantity polyoxyethylene N80 by recipe quantity, mix homogeneously adds 5% an amount of povidone solution system soft material, crosses 26 mesh sieves and granulates, and 40 ℃ of forced air dryings are complete;
3, with the polyoxyethylene N80 and the recipe quantity polyoxyethylene 303 of surplus, gaseous state silicon dioxide, magnesium stearate mix homogeneously;
4, treat particle drying back (pellet moisture is controlled in 2%) fully, 24 mesh sieve granulate, even with above-mentioned powder mixes, select the stamping of 7.5mm scrobicula.
Adopt the coating solution identical, and use and embodiment 1 identical coating and drilling method prepares present embodiment doxazosin controlled release tablet finished product with embodiment 1.
The mensuration of release
Sample thief, according to drug release determination method (two appendix X of Chinese Pharmacopoeia version in 2010 D, first method) (adopting the device of dissolution method second method), hydrochloric acid solution 900ml with 0.1M is a solvent, rotating speed is that per minute 75 changes, operation in accordance with the law, got solution 10ml respectively at the 1st hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, filter, and the instant hydrochloric acid solution 10ml that in process container, replenishes 0.1M, get subsequent filtrate as test liquid.It is an amount of that precision takes by weighing the doxazosin reference substance in addition, and the hydrochloric acid solution that adds 0.1M is mixed with 4 μ g/ml solution (using the methanol hydrotropy in case of necessity), product solution in contrast.Get test sample and reference substance solution, adopt high performance liquid chromatography (2010 editions two appendix IV D of Chinese Pharmacopoeia) to measure, calculate the burst size of every different time.Chromatographic condition is for being filler with octadecylsilane chemically bonded silica, water with acetonitrile-contain 0.5% acetic acid (V/V) and 0.25% triethylamine (V/V) (is got acetic acid 5mL and 2.5mL triethylamine, thin up is to 1000mL) (34: 66) be mobile phase, the detection wavelength is 246nm.
The measured value (%) of table 1. embodiment 1-3 doxazosin controlled release tablet release in vitro degree
The measured value (%) of table 2. embodiment 4-6 doxazosin controlled release tablet release in vitro degree
Claims (9)
1. doxazosin controlled release tablet, comprise the single-layer sheet heart and be wrapped in sheet coating membrane in the heart, and drug release hole is arranged in tablet one side, wherein the sheet heart contains the doxazosin and the polyoxyethylene of effective dose, and optionally contains or do not contain one or more acceptable accessories.
2. controlled release tablet as claimed in claim 1, wherein coating membrane is a semipermeable membrane, mainly contains cellulose acetate.
3. controlled release tablet as claimed in claim 1, sheet polyoxyethylene in the heart is selected from mean molecule quantity 4,000,000-7,000,000 and 100,000-300, at least a in 000.
4. controlled release tablet as claimed in claim 3, the sheet heart contains filler and penetrating agent.
5. controlled release tablet as claimed in claim 4, coating membrane also contains plasticizer and porogen.
6. controlled release tablet as claimed in claim 5, sheet filler and penetrating agent in the heart are lactose.
7. controlled release tablet as claimed in claim 6, plasticizer is a triethyl citrate in the coating membrane, porogen is a polyethylene glycol 1500.
8. controlled release tablet as claimed in claim 7, mean molecule quantity be 4,000,000-7, and 000,000 polyoxyethylene amount is 8%～23% of a tablet weight, mean molecule quantity is 100,000-300,000 polyoxyethylene amount is 19%～29% of a tablet weight.
9. controlled release tablet as claimed in claim 8, polyoxyethylated mean molecule quantity are respectively 100,000 and 7,000,000.
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| EP1293196A2 (en) * | 2001-09-14 | 2003-03-19 | Pharma Pass II LLC | Pharmaceutical composition comprising doxazosin |
| WO2006054152A1 (en) * | 2004-11-22 | 2006-05-26 | Ranbaxy Laboratories Limited | Monocompartment osmotic-controlled delivery system of doxazosin |
| CN101167728A (en) * | 2007-10-31 | 2008-04-30 | 合肥立方制药有限公司 | Doxazosin-mesylate controlled-releasing tablet and preparation method thereof |
| CN101912375A (en) * | 2010-08-26 | 2010-12-15 | 冯岩 | Metformin controlled release tablet |
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Application publication date: 20110518 |