CN1965817A - Sustained release tablet of glibenclamide and preparation process thereof - Google Patents
Sustained release tablet of glibenclamide and preparation process thereof Download PDFInfo
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- CN1965817A CN1965817A CN 200610022219 CN200610022219A CN1965817A CN 1965817 A CN1965817 A CN 1965817A CN 200610022219 CN200610022219 CN 200610022219 CN 200610022219 A CN200610022219 A CN 200610022219A CN 1965817 A CN1965817 A CN 1965817A
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Abstract
The invention relates to a Glibenclamide slow release tablet preparation which comprises effective dose of main constituent of Glibenclamide and medicinal auxiliary materials, the constituents include (by weight portion) Glibenclamide 0.5-5.0 parts, slow release material 20.0-170.0 parts, filling agent 5-100 parts, lubricating agent 5.0-30.0 parts, and right amount of binding agent. The invention also discloses the process for preparing the tablet preparation.
Description
Technical field
The present invention relates to medical technical field, relate in particular to a kind of sustained-release tablet preparation for the treatment of diabetes and preparation method thereof.
Background technology
Diabetes are a kind of whole body chronic metabolic disease by the gene decision, owing to the relative or absolute not enough disorder that causes sugar, fat and protein metabolism of insulin in the body; Its main feature is hyperglycemia and glycosuria, and often with severe complications such as hypertension, coronary heart disease etc.Prevalence in China's diabetes had ascendant trend year by year in the last few years, and patient age but descends to some extent.Have a strong impact on people's quality of life, increasing to people's physical and mental health harm, be second killer in the modern disease, tool is only second to cancer to the harm of human body.
Dietetic therapy is the base therapy method of all kinds glycosuria, and severe patient is oral antidiabetic drug or insulin simultaneously, or carries out pancreas transplantation.Oral antidiabetic drug commonly used clinically at present mainly contains sulfonylurea drugs (as: glipizide, glibenclamide, gliquidone), biguanides (as: metformin, insoral), alpha-glucosidase inhibitor (as: miglitol, Mitiglinide), euglycemic agent and Chinese patent medicine etc.Wherein glibenclamide is because consumption is few, and toxic and side effects is few and be widely used, and this product both can be used for unsatisfied heavy, the moderate patient of simple diet control separately, also can with biguanides share treatment single with biguanides control dissatisfied or long-term effect gastrointestinal disease patient; Also can share treatment IDDM (insulin dependent diabetes mellitus (IDDM)) patient, to reduce insulin dosage with insulin.
Glibenclamide, chemical name is: carbonyl N-[2-[4-[[[(hexamethylene amino)] amino] sulfonyl] phenyl] ethyl]-2-methoxyl group-5-chlorobenzamide.Molecular formula: C
23H
28ClN
3O
5S.Molecular weight: 494.01.
Its structural formula is:
Behind the oral administration, glibenclamide 95% is in gastrointestinal absorption.Peak reaching time of blood concentration is 3.2 ± 0.6 hours, and protein binding rate is 95%, at the liver intracellular metabolite, main metabolites be 4-anti--hydroxy derivatives, metabolite does not almost have hypoglycemic activity, respectively discharges 50% by gallbladder antiperspirant and urine, and it is 3.4 ± 2.9 hours that bibliographical information blood plasma is eliminated the half-life.
Studies show that glibenclamide belongs to the sulfonylurea oral hypoglycemic, the dominant mechanism of its hypoglycemic activity is to stimulate insulin, improves the sensitivity of surrounding tissue to insulin.But because the interior half-life of glibenclamide body is shorter, be 3-6 hour, the clinical oral administration ordinary preparation discharges and causes the back hypoglycemia of taking medicine too soon easily, and ordinary tablet is difficult to keep one day lasting mild blood sugar reducing function, and multiple dosing on the one is difficult to change of blood sugar rule in the estimated body, necessary monitor blood glucose concentration constantly, this has just brought many inconvenience to the patient, for keeping effective blood concentration, be necessary to develop its sustained-release preparation once-a-day, to obtain to continue mild release effect, avoid the release peak zone the hypoglycemia side effect.
Because the character of glibenclamide itself will be made the slow releasing preparation that suits the requirements and need solve many problems, as the ratio of principal agent amount, slow-release material, binding agent and lubricant and each component even preparation method etc.Only select reasonable raw material and proportioning thereof for use, the slow releasing preparation in strict accordance with certain method is made just can play the good slow release effect.
Summary of the invention
The prescription that the purpose of this invention is to provide a kind of glibenclamide sustained-release tablet preparation, peak time after this slow releasing tablet is oral, elimination half-life all obviously prolong, and single administration can effectively be controlled one day blood glucose, can reduce medicining times, bring convenience to the patient, reduce side effect simultaneously.
Another object of the present invention provides a kind of preparation method of above-mentioned glibenclamide sustained-release tablet preparation.
The technical solution adopted for the present invention to solve the technical problems is: a kind of glibenclamide sustained-release tablet preparation, principal agent glibenclamide and pharmaceutic adjuvant by effective dose are formed, pharmaceutic adjuvant wherein mainly comprises slow-release material, filler, lubricant and binding agent, and each ingredients weight parts proportioning is as follows: 0.5～5.0 part of glibenclamide, 20.0～170.0 parts of slow-release materials, 5～100 parts of filleies, 5.0～30.0 parts of lubricants, binding agent is an amount of.
The weight portion proportion optimization of above-mentioned each component is: 0.5～5.0 part of glibenclamide, and 20.0～85.0 parts of slow-release materials, 5～25 parts of filleies, 5.0～15.0 parts of lubricants, binding agent is an amount of.
It is good containing glibenclamide 0.5～5.0mg in every of the above-mentioned glibenclamide slow releasing tablet.
Slow-release material in the said components is good with hydrophilic skeleton slow-release material, can be selected from hydroxypropyl methylcellulose (HPMC), carbomer, methylcellulose (MC), ethyl cellulose (EC), polyvidone (PVP), polyethylene, polyoxy, the ethylene polypropylene, ethylene-vinyl acetate copolymer, hydroxyethyl-cellulose, sodium alginate, chitin, sodium chloride, polyvinyl alcohol, polystyrene, carbopol, Ka Bofei, polyphenyl vinyl chloride, octadecanol, glyceryl stearate, chitin, chitosan, diethyl phthalate, dioctyl phthalate, stearic acid, glucosan, Polyethylene Glycol, polypropylene, polysiloxanes, Brazil wax, spermaceti, zein, agar, sodium alginate, gelatin, Lac, pectin, you are gummy for melon, angle fork natural gum, locust bean gum, tragacanth, cholesterol, any one or more than one mixture in polyvinyl alcohol and the polyacrylic resin class etc.;
Filler in the said components can be selected from microcrystalline Cellulose (MCC), pregelatinized Starch, dextrin, sucrose, light magnesium oxide, calcium carbonate, glucose, lactose, calcium sulfate, sodium chloride, bicarbonate, dextrose, galactose, mannitol, mountain plough alcohol, xylitol, citric acid, tartaric acid, succinic acid, cholic acid, deoxycholic acid, ethylene glycol, polyethylene glycols, polyvidone class, surfactant-based poloxamer 188, the sodium lauryl sulphate of comprising; Microcrystalline Cellulose, protein-based as any one or more than one the mixture in casein, human albumin, bovine albumin, soybean protein, water osseocolla, the cyclodextrin etc.;
Lubricant in the said components can be selected from any one or more than one the mixture in stearic acid, calcium stearate, magnesium stearate, hydrogenated vegetable oil, micropowder silica gel or the Pulvis Talci etc.;
Above-mentioned binding agent can be selected from any one or more than one the mixture in hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, ethanol, PVP, syrup, rubber cement, the starch slurry etc.Generally be made into uses such as aqueous solution or alcoholic solution, add in preparation process, consumption seldom accounts for total formulation weight amount 1%～3%, and can be volatilized substantially in last dry run, and is minimum to the gross weight influence of preparation.
Hydroxypropyl methylcellulose in the above-mentioned slow-release material can be selected from following marque: 3cp, 5cp, 6cp, 15cp, 50cp, 4000cp, 10000cp, K100, K4M, K15M, K100M, E3, E5, E6, E50, E4M, E10M etc.;
Ethyl cellulose can be selected from following marque: 4cp, 7cp, 10cp, 20cp, 45cp, 100cp;
Polyethylene Glycol can be selected from following marque: 200,300,400,600,1000,1450,1500,2000,3350,4000,4600,6000,8000 etc.;
Carbomer can be selected from following marque: carbomer 934, carbomer 934 p, Acritamer 940, Carbopol 941, carbomer 980, carbomer 1342 etc.
Glibenclamide sustained-release tablet preparation of the present invention can be made into the common slow releasing tablet of non-constant release, and wherein each component and weight portion proportioning thereof are more preferably:
0.5～5.0 part of glibenclamide, 10～40 parts of (hydrophilic skeleton slow-release material) 100～130 parts of hydroxypropyl methylcellulose, ethyl cellulose or methylcellulose, 30～50 parts of (filler) microcrystalline Cellulose, 5～15 parts of (lubricant) Pulvis Talci; Binding agent is an amount of.
The surface of glibenclamide sustained-release tablet preparation of the present invention can also be covered with coating, with film coating is good, and thin film coating material can be selected from: cellulose acetate (CA), hydroxypropyl methylcellulose (HPMC), hyprolose (HPC), sodium carboxymethyl cellulose (CMC-Na), polyvidone (PVP), polyacrylic resin (I～IV number), the crosslinked polypropylene acid resin, AEA (AEA), Polyethylene Glycol (PEG), cellacefate (CAP), dibutyl phthalate (DBP), hydroxypropyl methylcellulose vinegar method ester (HPMCP), any one or more than one mixture in the acetic acid hydroxypropyl methylcellulose succinate (HPMCAS) etc.
Glibenclamide sustained-release tablet preparation of the present invention also can be made into the controlled release tablet of constant release, comprises label and coating two parts, and coat weight is 2～3% of a label weight;
Wherein each component of label and weight portion proportion optimization thereof are: 0.5～5.0 part of glibenclamide, and 90～120 parts of (hydrophilic skeleton slow-release material) NaCl, 60～100 parts of (filler) lactose, 5.0～10.0 parts of (lubricant) magnesium stearate, binding agent is an amount of;
Consisting of in following ratio of coating solution made: cellulose acetate 1.5～2.5g, and Macrogol 2000 1.0～2g, dibutyl phthalate 0.10～0.25g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
The common slow releasing tablet of the glibenclamide of above-mentioned non-constant release can prepare by following method:
Take by weighing the glibenclamide of described deal, add the slow-release material and the filler of described deal, mixing is all pulverized the back and is crossed 80～120 mesh sieves; Add suitable amount of adhesive, adopt dry method or wet granulation, granulate, add the lubricant mixing, use the tablet machine tabletting, make the tablet that contains effective principal agent amount and get final product.
The glibenclamide controlled release tablet of above-mentioned constant release can prepare by the method that comprises the steps:
(1), preparation label: take by weighing the glibenclamide of described deal, add the pharmaceutic adjuvant of described deal, mixing behind employing wet granulation, the granulate, is pressed into the monolayer label that contains effective principal agent amount; Perhaps powder directly is pressed into the label that contains effective principal agent amount;
(2), coating: with coating pan on the label that makes of (1) step evenly parcel one deck be added with the film-coat of porogen; Or do not add porogen, stamp the aperture that at least one diameter is 0.2～2.0mm with laser behind the coating; 30～60 ℃ of dryings, promptly.
Compared with prior art, the invention has the beneficial effects as follows: compare with existing glibenclamide conventional tablet, peak time after glibenclamide slow releasing tablet of the present invention is oral, elimination half-life all obviously prolong, single administration can effectively be controlled one day blood glucose, and blood sugar control regularly can more produce effect; Be fit to the blood glucose height, need the severe diabetes patient of the basic blood glucose of long-time control, also can effectively control post-prandial glycemia.The present invention can reduce and takes number of times, and only need take once every day, brings convenience to the patient, reduces side effect simultaneously, can reach the lasting mild purpose of drug effect again.
Description of drawings
Fig. 1 is the external stripping curve figure of glibenclamide ordinary tablet.
Fig. 2 is the external stripping curve figure of the common slow releasing tablet of the glibenclamide of the embodiment of the invention 1.
Fig. 3 is the external stripping curve figure of the glibenclamide controlled release tablet of the embodiment of the invention 6.
Fig. 4 is the common relatively sketch map of the external stripping curve of the glibenclamide controlled release tablet of releasing the sheet and the embodiment of the invention 6 of painting of the glibenclamide of glibenclamide ordinary tablet, the embodiment of the invention 1.
In Fig. 4, the 1st, the external stripping curve of glibenclamide ordinary tablet, the 2nd, the external stripping curve of the common slow releasing tablet of the embodiment of the invention 1 glibenclamide, the 3rd, the external stripping curve of the embodiment of the invention 6 glibenclamide controlled release tablet.
The specific embodiment
The present invention is described in further detail below in conjunction with the specific embodiment.
But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made include within the scope of the invention.
Embodiment 1
Present embodiment is the common slow releasing tablet of the glibenclamide of non-constant release, and wherein each component and weight portion proportioning thereof are:
1 part of glibenclamide, 125 parts of hydroxypropyl methylcellulose (K4M), 25 parts of ethyl celluloses, 40 parts of microcrystalline Cellulose, 9 parts of Pulvis Talci, PVP an amount of (be made into 10% alcoholic solution make binding agent).
The present embodiment preparation method is as follows:
Take by weighing glibenclamide, hydroxypropyl methylcellulose, ethyl cellulose and the microcrystalline Cellulose of described deal, mixing is all pulverized the back and is crossed 80～120 mesh sieves; Add an amount of PVP10% alcoholic solution, adopt wet granulation, with 18 mesh sieve granulate, 40～60 ℃ of dryings were taken out after 1～3 hour; The Pulvis Talci that adds described deal, mixing after the mixed powder drug content of test is qualified, is used the tablet machine tabletting, makes the heavy 0.2g of sheet, every slow releasing tablet that contains principal agent 1mg, promptly.
Present embodiment is the common slow releasing tablet of the glibenclamide of non-constant release, and wherein each component and weight portion proportioning thereof are:
2.5 parts of glibenclamide, 110 parts of hydroxypropyl methylcellulose (K4M), 35 parts of methylcellulose, 35 parts of microcrystalline Cellulose, 5 parts of Pulvis Talci, hydroxypropyl methylcellulose an amount of (be made into 5% aqueous solution make binding agent).
The present embodiment preparation method is as follows:
Take by weighing glibenclamide, hydroxypropyl methylcellulose (K4M), methylcellulose and the microcrystalline Cellulose of described deal, mixing is all pulverized the back and is crossed 80～120 mesh sieves; Add an amount of hydroxypropyl methylcellulose 5% aqueous solution, make wet grain, with 18 mesh sieve granulate, 40～60 ℃ of dryings were taken out after 2～4 hours; The Pulvis Talci that adds described deal, mixing after the mixed powder drug content of test is qualified, is used the tablet machine tabletting, makes the heavy 0.2g of sheet, every slow releasing tablet that contains principal agent 2.5mg, promptly.
Embodiment 3
Present embodiment is the common slow releasing tablet of the glibenclamide of non-constant release, and wherein each component and weight portion proportioning thereof are:
5 parts of glibenclamide, 75 parts of Brazil waxs, 10 parts of hydrogenated vegetable oils, 20 parts in calcium sulfate, 12 parts in mannitol, 50 parts of ethyl celluloses, 12 parts of Stepanol MGs, 15 parts of magnesium stearate, sodium alginate an amount of (be made into 5% aqueous solution make binding agent).
The present embodiment preparation method is as follows:
Take by weighing glibenclamide, Brazil wax, hydrogenated vegetable oil, calcium sulfate, mannitol, sodium alginate, ethyl cellulose, Stepanol MG and the magnesium stearate of described deal, glibenclamide is joined in the mixture of the Brazil wax of fusing and castor oil hydrogenated, put coldly, levigate after the stirring, cross 80 mesh sieves; Add calcium sulfate, mannitol, magnesium stearate, ethyl cellulose, be mixed, making binding agent with an amount of sodium alginate 5% aqueous solution granulates, dry, granulate, after adding formula ratio Stepanol MG mixes, the tablet machine tabletting, make the heavy 0.2g of sheet, every slow releasing tablet that contains principal agent 5.0mg, promptly.
Present embodiment is the common slow releasing tablet of the glibenclamide of non-constant release, and wherein each component and weight portion proportioning thereof are:
2 parts of glibenclamide, 125.0 parts of hyprolose, 3.5 parts of polyvidones, 45.0 parts of lactose, 15 parts of magnesium stearate, PVP an amount of (be made into 10% alcoholic solution make binding agent).
The present embodiment preparation method is as follows:
Take by weighing glibenclamide, hyprolose, polyvidone, lactose and the magnesium stearate of described deal, mixing is all pulverized the back and is crossed 80～120 mesh sieves; Add an amount of PVP10% alcoholic solution, make wet grain, 40～60 ℃ of dryings were taken out after 2～4 hours, with 18 mesh sieve granulate, the Pulvis Talci that adds described deal, mixing is after the mixed powder drug content of test is qualified, use the tablet machine tabletting, make the heavy 0.2g of sheet, every slow releasing tablet that contains principal agent 2mg, promptly.
Embodiment 5
Present embodiment is the common slow releasing tablet of the glibenclamide of non-constant release, and wherein each component and weight portion proportioning thereof are:
0.5 part of glibenclamide, 145 parts of carbopol (Carrboro 974P-NF), 20 parts of ethyl celluloses, 20 parts of micropowder silica gels (Syloid 244), 10 parts of magnesium stearate, PVP an amount of (be made into 10% alcoholic solution make binding agent).
The present embodiment preparation method is as follows:
Take by weighing glibenclamide, carbopol, ethyl cellulose and the polyvidone of described deal, cross 80 mesh sieves behind the mixing, add an amount of polyvidone 10% ethanol liquid, make soft material, crossing 20 mesh sieves granulates, 60 ℃ of dryings, granulate, 80 mesh sieves are removed fine powder, the micropowder silica gel and the magnesium stearate that add described deal, tabletting behind the mix homogeneously is made the heavy 0.2g of sheet, every slow releasing tablet that contains principal agent 0.5mg, promptly.
The glibenclamide slow releasing tablet of the foregoing description 1-5 is the common slow releasing tablet of non-constant release.
The glibenclamide slow releasing tablet of following embodiment 6-9 is the controlled release tablet of constant release.
Present embodiment is the glibenclamide controlled release tablet of constant release, comprises label and coating two parts, and coat weight is 2.5% of a label weight;
Wherein each component of label and weight portion proportion optimization thereof are: 5.0 parts of glibenclamide, 105 parts of NaCl, 85 parts of lactose, 5.0 parts of magnesium stearate, PVP an amount of (be made into 10% alcoholic solution make binding agent);
Consisting of in following ratio of coating solution made: cellulose acetate 2.0g, and Macrogol 2000 1.5g, dibutyl phthalate 0.15g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
The present embodiment preparation method is as follows:
(1), preparation label: the glibenclamide, NaCl and the lactose that take by weighing described deal, cross mixing behind 80 mesh sieves respectively, add an amount of PVP10% alcoholic solution, make soft material behind the mixing, granulate with 20 mesh sieves, about 60 ℃ of dryings, reuse 20 mesh sieve granulate add the magnesium stearate of described deal, tabletting behind the mix homogeneously, control hardness is 5 ± 0.5N, makes the heavy 0.2g of sheet, every label that contains glibenclamide 5mg;
(2), coating: first preparation coating solution: get cellulose acetate, Macrogol 2000 and the dibutyl phthalate of described deal, the volume ratio that joins described deal is that mixing promptly makes coating solution in acetone-alcohol mixed solvent of 2: 1; The label that makes of (1) step weighed be placed in the coating pan, art for coating according to routine, rotate with 50 rotating speeds that change per minute, be blown into the about 10min of hot-air preheating, when treating that the label temperature is about 40 ℃, coating continued to be blown into hot-air 30 minutes to increasing weight 2.5%, then that coated tablet is dry under 40 ℃ in drying baker, promptly.
Embodiment 7
Present embodiment is the glibenclamide controlled release tablet of constant release, comprises label and coating two parts, and coat weight is 2% of a label weight;
Wherein each component of label and weight portion proportion optimization thereof are: 2.0 parts of glibenclamide, 115 parts of NaCl, 75 parts of microcrystalline Cellulose, 8.0 parts of calcium stearates, PVP an amount of (be made into 10% alcoholic solution make binding agent);
Consisting of in following ratio of coating solution made: cellulose acetate 2.0g, and Macrogol 2000 1.5g, cellacefate 0.20g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
The present embodiment preparation method is as follows:
(1), preparation label: the glibenclamide, NaCl and the microcrystalline Cellulose that take by weighing described deal, cross 80 mesh sieves respectively, mixing adds an amount of PVP10% alcoholic solution, make soft material, 20 mesh sieves are granulated, about 50 ℃ of dryings, 20 mesh sieve granulate, the calcium stearate that adds described deal, tabletting behind the mix homogeneously, control hardness is 5 ± 0.5N, makes the heavy 0.2g of sheet, every label that contains glibenclamide 2mg;
(2), coating: prepare coating solution earlier: get cellulose acetate, Macrogol 2000 and the cellacefate of described deal, the volume ratio that joins described deal is that mixing promptly makes coating solution among 2: 1 acetone-alcohol mixed solvent 100ml; The label that makes of (1) step weighed be placed in the coating pan, art for coating according to routine, rotate with 50 rotating speeds that change per minute, be blown into the about 10min of hot-air preheating, when treating that the label temperature is about 40 ℃, coating continued to be blown into hot-air 30 minutes to increasing weight 2.5%, then that coated tablet is dry under 40 ℃ in drying baker, promptly.
Present embodiment is the glibenclamide controlled release tablet of constant release, comprises label and coating two parts, and coat weight is 3% of a label weight;
Wherein each component of label and weight portion proportion optimization thereof are: 0.5 part of glibenclamide, NaHCO
3100 parts, 95 parts in dextrin, 2.5 parts of magnesium stearate, PVP an amount of (be made into 10% alcoholic solution make binding agent);
Consisting of in following ratio of coating solution made: cellulose acetate 3.0g, and dibutyl phthalate 0.25g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
The present embodiment preparation method is as follows:
(1), preparation label: the glibenclamide, the NaHCO that take by weighing described deal
3And dextrin, cross mixing behind 80 mesh sieves respectively, add an amount of PVP10% alcoholic solution, make soft material behind the mixing, granulate with 20 mesh sieves, about 60 ℃ of dryings, reuse 20 mesh sieve granulate add the magnesium stearate of described deal, tabletting behind the mix homogeneously, control hardness is 5 ± 0.5N, makes the heavy 0.2g of sheet, every label that contains glibenclamide 0.5mg;
(2), coating: prepare coating solution earlier: get the cellulose acetate and the dibutyl phthalate of described deal, the volume ratio that joins described deal is that mixing promptly makes coating solution among 2: 1 acetone-alcohol mixed solvent 100ml; The label that makes of (1) step weighed be placed in the coating pan, art for coating according to routine, rotate with 50 rotating speeds that change per minute, be blown into the about 10min of hot-air preheating, when treating that the label temperature is about 40 ℃, coating is to increasing weight 3%, continued to be blown into hot-air 30 minutes, then that coated tablet is dry under 40 ℃ in drying baker, stamp the aperture that diameter is 0.25mm on the coated tablet surface with laser-beam drilling machine, promptly.
Embodiment 9
Present embodiment is the glibenclamide controlled release tablet of constant release, comprises label and coating two parts, and coat weight is 2.5% of a label weight;
Wherein each component of label and weight portion proportion optimization thereof are: 1.0 parts of glibenclamide, 105 parts of NaCl, 85 parts of lactose, 4.0 parts of magnesium stearate, PVP an amount of (be made into 10% alcoholic solution make binding agent);
Consisting of in following ratio of coating solution made: polyacrylic resin IV 3g, and dibutyl phthalate 0.25g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
The present embodiment preparation method is as follows:
(1), preparation label: the glibenclamide, NaCl and the lactose that take by weighing described deal, cross mixing behind 80 mesh sieves respectively, add an amount of PVP10% alcoholic solution, make soft material behind the mixing, granulate with 20 mesh sieves, about 60 ℃ of dryings, reuse 20 mesh sieve granulate add the magnesium stearate of described deal, tabletting behind the mix homogeneously, control hardness is 5 ± 0.5N, makes the heavy 0.2g of sheet, every label that contains glibenclamide 1mg;
(2), coating: prepare coating solution earlier: get the polyacrylic resin IV and the dibutyl phthalate of described deal, the volume ratio that joins described deal is that mixing promptly makes coating solution among 2: 1 acetone-alcohol mixed solvent 100ml; The label that makes of (1) step weighed be placed in the coating pan, art for coating according to routine, rotate with 50 rotating speeds that change per minute, be blown into the about 10min of hot-air preheating, when treating that the label temperature is about 40 ℃, coating is to increasing weight 2.5%, continued to be blown into hot-air 30 minutes, then that coated tablet is dry under 40 ℃ in drying baker, respectively stamp the aperture that diameter is 0.5mm with laser-beam drilling machine in both sides, coated tablet surface, promptly.
In order to investigate the slow release effect of glibenclamide slow releasing tablet of the present invention, the inventor gets common glibenclamide sheet (Tianjin Medicine Research Academy Pharmaceutical Co., Ltd, lot number: 021018,2.5mg/ sheet), the common slow releasing tablet of glibenclamide sheet of the embodiment of the invention 1 and the glibenclamide sheet controlled release tablet of embodiment 6 have been carried out the release test, adopt following external dissolving-out method: get the glibenclamide slow releasing tablet, adopt little agar diffusion method (three therapeutic methods of traditional Chinese medicine among 2005 editions appendix XC of Chinese Pharmacopoeia), tris solution 100ml with 0.02% is a dissolution medium, and Revolution Per Minute 50 changes, in accordance with the law operation, 1,2,4,6,8, got pastille medium 5ml in 10,12 hours respectively, 0.45 μ m filtering with microporous membrane, it is to be tested in right amount to get subsequent filtrate, and additional medium 5ml; Measure its trap at the 229nm place with quartz colorimetric utensil, and on standard curve, read its content, and obtain stripping percentage ratio, plot external stripping curve figure.Result of the test is seen Fig. 1-4 respectively.
The result shows: common slow releasing tablet of glibenclamide sheet of the present invention and glibenclamide sheet controlled release tablet all can play slow releasing function significantly, and medicine peak time, elimination half-life all obviously prolong, and drug effect is sustainable more than 12 hours.
Claims (9)
1. glibenclamide sustained-release tablet preparation, principal agent glibenclamide and pharmaceutic adjuvant by effective dose are formed, it is characterized in that: described pharmaceutic adjuvant mainly comprises slow-release material, filler, lubricant and binding agent, and each ingredients weight parts proportioning is as follows: 0.5～5.0 part of glibenclamide, 20.0～170.0 parts of slow-release materials, 5～100 parts of filleies, 5.0～30.0 parts of lubricants, binding agent is an amount of.
2. glibenclamide sustained-release tablet preparation according to claim 1, it is characterized in that: weight proportion part of described each component is: 0.5～5.0 part of glibenclamide, 20.0～85.0 parts of slow-release materials, 5～25 parts of filleies, 5.0～15.0 parts of lubricants, binding agent is an amount of.
3. glibenclamide sustained-release tablet preparation according to claim 1 and 2 is characterized in that: contain glibenclamide 0.5～5.0mg in every of the described glibenclamide slow releasing tablet.
4. glibenclamide sustained-release tablet preparation according to claim 1 is characterized in that:
Described slow-release material is selected from hydroxypropyl methylcellulose, carbomer, methylcellulose, ethyl cellulose, polyvidone, polyethylene, polyoxy, the ethylene polypropylene, ethylene-vinyl acetate copolymer, hydroxyethyl-cellulose, sodium alginate, chitin, sodium chloride, polyvinyl alcohol, polystyrene, carbopol, Ka Bofei, polyphenyl vinyl chloride, octadecanol, glyceryl stearate, chitin, chitosan, diethyl phthalate, dioctyl phthalate, stearic acid, glucosan, Polyethylene Glycol, polypropylene, polysiloxanes, Brazil wax, spermaceti, zein, agar, sodium alginate, gelatin, Lac, pectin, you are gummy for melon, angle fork natural gum, locust bean gum, tragacanth, cholesterol, any one or more than one the mixture of polyvinyl alcohol and polyacrylic resin apoplexy due to endogenous wind;
Described filler is selected from microcrystalline Cellulose, pregelatinized Starch, dextrin, sucrose, light magnesium oxide, calcium carbonate, glucose, lactose, calcium sulfate, sodium chloride, bicarbonate, dextrose, galactose, mannitol, mountain plough alcohol, xylitol, citric acid, tartaric acid, succinic acid, cholic acid, deoxycholic acid, ethylene glycol, polyethylene glycols, polyvidone class, surfactant-based poloxamer 188, the sodium lauryl sulphate of comprising; Microcrystalline Cellulose, protein-based as any one or more than one the mixture in casein, human albumin, bovine albumin, soybean protein, water osseocolla, the cyclodextrin;
Described lubricant is selected from any one or more than one the mixture in stearic acid, calcium stearate, magnesium stearate, hydrogenated vegetable oil, micropowder silica gel or the Pulvis Talci;
Described binding agent is selected from any one or more than one the mixture in hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, ethanol, PVP, syrup, rubber cement, the starch slurry.
5. glibenclamide sustained-release tablet preparation according to claim 1, it is characterized in that: each component and weight portion proportioning thereof are in the described glibenclamide sustained-release tablet preparation: 0.5～5.0 part of glibenclamide, 10～40 parts of 100～130 parts of hydroxypropyl methylcellulose, ethyl cellulose or methylcellulose, 30～50 parts of microcrystalline Cellulose, 5～15 parts of Pulvis Talci, binding agent is an amount of.
6. glibenclamide sustained-release tablet preparation according to claim 1, it is characterized in that: described dosage surface also is covered with coating, and described coating material is selected from: any one or more than one the mixture in cellulose acetate, hydroxypropyl methylcellulose, hyprolose, sodium carboxymethyl cellulose, polyvidone, polyacrylic resin I～IV number, crosslinked polypropylene acid resin, AEA, Polyethylene Glycol, cellacefate, dibutyl phthalate, hydroxypropyl methylcellulose vinegar method ester, the acetic acid hydroxypropyl methylcellulose succinate.
7. according to claim 1 or 6 described glibenclamide sustained-release tablet preparations, it is characterized in that:
Described glibenclamide sustained-release tablet preparation comprises label and coating two parts, and coat weight is 2～3% of a label weight;
Wherein each component of label and weight portion proportioning thereof are: 0.5～5.0 part of glibenclamide, and 90～120 parts of NaCl, 60～100 parts of lactose, 5.0～10.0 parts of magnesium stearate, binding agent is an amount of;
Consisting of in following ratio of coating solution made: cellulose acetate 1.5～2.5g, and Macrogol 2000 1.0～2g, dibutyl phthalate 0.10～0.25g, volume ratio is acetone-alcohol mixed solvent 100ml of 2: 1.
8. the preparation method of the described glibenclamide sustained-release tablet preparation of claim 5 is characterized in that:
Take by weighing the glibenclamide of described deal, add the slow-release material and the filler of described deal, mixing is all pulverized the back and is crossed 80～120 mesh sieves; Add suitable amount of adhesive, adopt dry method or wet granulation, granulate, add the lubricant mixing of described deal, use the tablet machine tabletting, make the tablet that contains effective principal agent amount and get final product.
9. the preparation method of the described glibenclamide sustained-release tablet preparation of claim 7 comprises the steps:
(1), preparation label: take by weighing the glibenclamide of described deal, add the pharmaceutic adjuvant of described deal, mixing behind employing wet granulation, the granulate, is pressed into the monolayer label that contains effective principal agent amount; Perhaps powder directly is pressed into the label that contains effective principal agent amount;
(2), coating: with coating pan on the label that makes of (1) step evenly parcel one deck be added with the film-coat of porogen; Or do not add porogen, stamp the aperture that at least one diameter is 0.2～2.0mm with laser behind the coating; 30～60 ℃ of dryings, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610022219 CN1965817A (en) | 2006-11-08 | 2006-11-08 | Sustained release tablet of glibenclamide and preparation process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610022219 CN1965817A (en) | 2006-11-08 | 2006-11-08 | Sustained release tablet of glibenclamide and preparation process thereof |
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| CN1965817A true CN1965817A (en) | 2007-05-23 |
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| CN 200610022219 Pending CN1965817A (en) | 2006-11-08 | 2006-11-08 | Sustained release tablet of glibenclamide and preparation process thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098489A (en) * | 2014-07-10 | 2014-10-15 | 沈阳药科大学 | Micronized glibenclamide and composition thereof |
| CN104490755A (en) * | 2014-12-05 | 2015-04-08 | 海南卫康制药(潜山)有限公司 | Lyophilized tablet prepared from glyburide composition and preparation method thereof |
| CN106511562A (en) * | 2017-01-12 | 2017-03-22 | 卢正良 | Traditional Chinese medicine for treating cardiovascular diseases |
| CN112603906A (en) * | 2020-12-30 | 2021-04-06 | 南京都盟消防技术有限公司 | Microcapsule framework material and preparation method thereof |
| CN117257747A (en) * | 2023-11-21 | 2023-12-22 | 泊诺(天津)创新医药研究有限公司 | Bupropion hydrochloride tablet and preparation method thereof |
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2006
- 2006-11-08 CN CN 200610022219 patent/CN1965817A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098489A (en) * | 2014-07-10 | 2014-10-15 | 沈阳药科大学 | Micronized glibenclamide and composition thereof |
| CN104490755A (en) * | 2014-12-05 | 2015-04-08 | 海南卫康制药(潜山)有限公司 | Lyophilized tablet prepared from glyburide composition and preparation method thereof |
| CN106511562A (en) * | 2017-01-12 | 2017-03-22 | 卢正良 | Traditional Chinese medicine for treating cardiovascular diseases |
| CN112603906A (en) * | 2020-12-30 | 2021-04-06 | 南京都盟消防技术有限公司 | Microcapsule framework material and preparation method thereof |
| CN117257747A (en) * | 2023-11-21 | 2023-12-22 | 泊诺(天津)创新医药研究有限公司 | Bupropion hydrochloride tablet and preparation method thereof |
| CN117257747B (en) * | 2023-11-21 | 2024-01-30 | 泊诺(天津)创新医药研究有限公司 | Bupropion hydrochloride tablet and preparation method thereof |
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Open date: 20070523 |