CN105030793A - Metformin hydrochloride and glibenclamide capsule and preparation method thereof - Google Patents
Metformin hydrochloride and glibenclamide capsule and preparation method thereof Download PDFInfo
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- CN105030793A CN105030793A CN201510528094.4A CN201510528094A CN105030793A CN 105030793 A CN105030793 A CN 105030793A CN 201510528094 A CN201510528094 A CN 201510528094A CN 105030793 A CN105030793 A CN 105030793A
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- glibenclamide
- metformin
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- 229960004580 glibenclamide Drugs 0.000 title claims abstract description 53
- 239000002775 capsule Substances 0.000 title claims abstract description 48
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 title claims abstract description 33
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 title claims abstract description 29
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 229960004329 metformin hydrochloride Drugs 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000000945 filler Substances 0.000 claims abstract description 17
- 239000000314 lubricant Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 239000008187 granular material Substances 0.000 claims description 25
- 239000011230 binding agent Substances 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 19
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 14
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 14
- 229920000881 Modified starch Polymers 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000010348 incorporation Methods 0.000 claims description 9
- 239000007779 soft material Substances 0.000 claims description 9
- 235000021355 Stearic acid Nutrition 0.000 claims description 8
- 239000004744 fabric Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 8
- 239000008117 stearic acid Substances 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 229960003943 hypromellose Drugs 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 239000005995 Aluminium silicate Substances 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 235000012211 aluminium silicate Nutrition 0.000 claims description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 235000010216 calcium carbonate Nutrition 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 235000011132 calcium sulphate Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229950005770 hyprolose Drugs 0.000 claims description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 238000005453 pelletization Methods 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 9
- 238000004090 dissolution Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 4
- 229960003105 metformin Drugs 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009506 drug dissolution testing Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 229940125396 insulin Drugs 0.000 description 1
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- 230000007774 longterm Effects 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the technical field of medicines and particularly relates to a metformin hydrochloride and glibenclamide capsule and a preparation method thereof. The metformin hydrochloride and glibenclamide capsule is prepared from the following raw materials in parts by weight: 200-300 parts of metformin hydrochloride, 1.0-1.5 parts of glibenclamide, 44-135 parts of filler, 2.5-7.5 parts of adhesive and 0.5-1.5 parts of lubricant. The process provided by the invention is simple and easy to implement, and the prepared metformin hydrochloride and glibenclamide capsule has the advantages of steady release and high dissolution rate.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of metformin-glibenclamide capsule and preparation method thereof.
Background technology
Diabetes are No. second diseases being only second to cardiovascular disease, and WHO survey result shows, and there is several hundred million diabetics in the current whole world, and wherein 90% is patients with NIDDM.
Because metformin can strengthen the sensitivity of tissue to insulin, reduce the generation of glucose, there is certain synergism with sulfonamides oral antidiabetic drug, also can slow down the out-of-service time of sulfonamides orally-taken blood sugar reducing medicine.Metformin can affect the complication process of diabetes to a certain extent, improves lipid metabolism, also has good improvement result to the body weight of diabetics, particularly obese type patients with NIDDM is more advocated in early days to using metformin.
Treatment due to diabetes is a long-term process, and various medicine all exists body toleration, and therefore service time is longer, and curative effect is poorer, and sulfonamides orally-taken blood sugar reducing medicine is particularly evident.Generally advocate use in conjunction different types of hypoglycemic medicine clinically, wherein studying the most deep is exactly the use in conjunction of sulfa drugs and metformin.
Although disclose metformin-glibenclamide oral formulations in existing technology, as metformin-glibenclamide sheet, metformin-glibenclamide capsule etc., but the restriction owing to being subject to the conditions such as technique, technology, equipment produced by existing capsule, the Species differences of capsule, uniformity of dosage units, dissolution are wayward, poor stability.
Publication number is that the patent of invention of CN101757002A discloses a kind of metformin-glibenclamide capsule and preparation method, and a kind of weight differential, uniformity of dosage units can be provided controlled, and dissolving out capability is excellent, stay-in-grade metformin-glibenclamide capsule.But its preparation process needs special charging gear, higher to the requirement of equipment.
Summary of the invention
The object of this invention is to provide a kind of metformin-glibenclamide capsule, drug release is steady, and weight differential is controlled, and dissolving out capability is excellent, steady quality; Invention also provides the preparation method of metformin-glibenclamide capsule, scientific and reasonable, simple.
Metformin-glibenclamide capsule of the present invention, be made up of the raw material of following parts by weight:
Metformin hydrochloride 200-300 part
Glibenclamide 1.0-1.5 part
Filler 44-135 part
Binding agent 2.5-7.5 part
Lubricant 0.5-1.5 part.
Described filler is one or more in starch, dextrin, lactose, microcrystalline Cellulose, sucrose, mannitol, sorbitol, pregelatinized Starch, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, xylose, Kaolin or sodium chloride, is preferably pregelatinized Starch.
Described binding agent is one or more in water, wax, alcohol, polyvidone, starch, hypromellose, methylcellulose, ethyl cellulose, sucrose, sodium carboxymethyl cellulose, gelatin, sodium alginate, hyprolose or Polyethylene Glycol, is preferably polyvidone.
When binding agent is polyvidone, the solution that wet granulation binding agent used is formed for polyvidone and dehydrated alcohol, the mass percent concentration of polyvidone is 5-15%, and the consumption of povidone solution is 25-75 part.
Described lubricant is one or more in silicon dioxide, magnesium stearate, stearic acid, Pulvis Talci, hydrogenated vegetable oil or Polyethylene Glycol, is preferably stearic acid.
The preparation method of metformin-glibenclamide capsule of the present invention, step is as follows:
(1) metformin hydrochloride, glibenclamide and filler pulverize and sieve;
(2) metformin hydrochloride, glibenclamide and the filler handled well is taken;
(3) load weighted metformin hydrochloride, glibenclamide and filler are joined wet granulator, after mix homogeneously, add binding agent and prepare soft material, granulate with screen cloth;
(4) material that step (3) obtains is added Fluidbedgranulatingdrier drying;
(5) material that step (4) obtains is added in pelletizing machine, use screen cloth granulate;
(6) material and lubricant that step (5) obtains is taken;
(7) material load weighted step (5) obtained and lubricant, join in mixer and mix;
(8) material of step (7) gained is added capsule filler and carry out capsule charge.
The order number of the sieve described in step (1) is 60-120 order.
The order number of the screen cloth described in step (3) is 14-30 order.
The order number of the screen cloth described in step (5) is 14-30 order.
Incorporation time described in step (7) is 5-30min.
Do not need special charging gear in preparation process of the present invention, use common capsule filling machine to realize yet.
The present invention is by selecting kind and the consumption of suitable filler, binding agent, lubricant, and in preparation process, supplementary material sieves the screening of the conditions such as order number, and obtained capsule has the advantages such as dissolution is good, content uniformity is little.
The present invention compared with prior art, has following beneficial effect:
Present invention process is simple, easy to implement, and the metformin-glibenclamide capsule drug release prepared is steady, and dissolution is high.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described further.
In embodiment and comparative example, in all forms, " N/A " represents and does not add.
Embodiment 1-6
Metformin hydrochloride, glibenclamide, filler pulverized 80 mesh sieves.Take metformin hydrochloride 2500g, glibenclamide 12.5g, filler 900g, mix homogeneously.Take polyvidone 50g, add 450g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3462.5g and stearic acid 10g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
The kind of the filler that embodiment 1-6 is used and consumption and related performance indicators are in table 1.
Data as can be seen from table 1, embodiment 4 best performance.
The kind of the filler that table 1 embodiment 1-6 is used and consumption and related performance indicators
Embodiment 7-10
Metformin hydrochloride, glibenclamide, pregelatinized Starch pulverized 80 mesh sieves.Take metformin hydrochloride 2500g, glibenclamide 12.5g, pregelatinized Starch 900g, mix homogeneously.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3462.5g and stearic acid 10g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
The performance of the product of the kind of the binding agent that embodiment 7-10 is used and consumption and preparation is in table 2.
Data as can be seen from table 2, embodiment 8 best performance.
The performance of the product of the kind of the binding agent that table 2 embodiment 7-10 is used and consumption and preparation
Embodiment 11-14
Metformin hydrochloride, glibenclamide, pregelatinized Starch pulverized 80 mesh sieves.Take metformin hydrochloride 2500g, glibenclamide 12.5g, pregelatinized Starch 900g, mix homogeneously.Take polyvidone 50g, add 450g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3462.5g and lubricant, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
The performance of the product of the kind of the lubricant that embodiment 11-14 is used and consumption and preparation is in table 3.
Data as can be seen from table 3, embodiment 12 best performance.
The performance of the product of the kind of the binding agent that table 3 embodiment 11-14 is used and consumption and preparation
Embodiment 15-17
Metformin hydrochloride, glibenclamide, pregelatinized Starch pulverize and sieve.Take metformin hydrochloride 2500g, glibenclamide 12.5g, pregelatinized Starch 900g, mix homogeneously.Take polyvidone 50g, add 450g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3462.5g and stearic acid 10g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
Comparative example 1
Preparation method is identical with embodiment 15-17, and difference is that supplementary material used does not pulverize and sieve.
The performance of the product of embodiment 15-17 and comparative example 1 supplementary material granularity used and preparation is in table 4.
Data as can be seen from table 4, embodiment 17 best performance.
The performance of the product of table 4 embodiment 15-17 and comparative example 1 supplementary material granularity used and preparation
Embodiment 18
Embodiment 18 supplementary material used is in table 5.
Table 5 embodiment 18 supplementary material used
| Metformin hydrochloride | 2500g |
| Glibenclamide | 12.5g |
| Pregelatinized Starch | 440g |
| Polyvidone | 25g |
| Stearic acid | 5g |
| Preparation | 10000 |
Preparation technology:
Metformin hydrochloride, glibenclamide, pregelatinized Starch pulverized 80 mesh sieves.Take metformin hydrochloride 2500g, glibenclamide 12.5g, pregelatinized Starch 440g, mix homogeneously.Take polyvidone 25g, add 225g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 2977.5g and stearic acid 5g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
Embodiment 19
Embodiment 19 supplementary material used is in table 6.
Table 6 embodiment 19 supplementary material used
| Metformin hydrochloride | 2500g |
| Glibenclamide | 12.5g |
| Microcrystalline Cellulose | 880g |
| Polyvidone | 50g |
| Magnesium stearate | 10g |
| Preparation | 10000 |
Preparation technology:
Metformin hydrochloride, glibenclamide, pregelatinized Starch pulverized 80 mesh sieves.Take metformin hydrochloride 2500g, glibenclamide 12.5g, microcrystalline Cellulose 880g, mix homogeneously.Take polyvidone 50g, add 450g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3442.5g and magnesium stearate 10g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
Embodiment 20
Embodiment 20 supplementary material used is in table 7.
Table 7 embodiment 20 supplementary material used
| Metformin hydrochloride | 2500g |
| Glibenclamide | 12.5g |
| Lactose | 1320g |
| Hypromellose | 15g |
| Polyethylene Glycol | 15g |
| Preparation | 10000 |
Preparation technology:
80 mesh sieves pulverized by metformin hydrochloride, glibenclamide, lactose.Take metformin hydrochloride 2500g, glibenclamide 12.5g, lactose 1320g, mix homogeneously.Take hypromellose 15g, add 650g dehydrated alcohol, make solution and make binding agent.Binding agent is joined in said mixture and prepares soft material, granulate with 20 eye mesh screens.Use Fluidbedgranulatingdrier is dry.Use rocking type granule-finishing machine 20 eye mesh screen granulate, add in mixer by granule 3847.5g and Polyethylene Glycol 15g, incorporation time is 10 minutes.Capsule fill is carried out with capsule filling machine.
The stripping curve of embodiment 18-20 sample is have detected according to national Bureau of Drugs Supervision standard YBH12092004.Data as can be seen from table 8-9, it is good that metformin-glibenclamide capsule prepared by the present invention has dissolution, the advantage that relative average debiation is little.
Table 8 metformin-glibenclamide capsule dissolution testing result
Table 9 metformin-glibenclamide capsule dissolution testing result
Claims (9)
1. a metformin-glibenclamide capsule, is characterized in that being made up of the raw material of following parts by weight:
2. metformin-glibenclamide capsule according to claim 1, is characterized in that described filler is one or more in starch, dextrin, lactose, microcrystalline Cellulose, sucrose, mannitol, sorbitol, pregelatinized Starch, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, xylose, Kaolin or sodium chloride.
3. metformin-glibenclamide capsule according to claim 1, is characterized in that described binding agent is one or more in water, wax, alcohol, polyvidone, starch, hypromellose, methylcellulose, ethyl cellulose, sucrose, sodium carboxymethyl cellulose, gelatin, sodium alginate, hyprolose or Polyethylene Glycol.
4. metformin-glibenclamide capsule according to claim 1, is characterized in that described lubricant is one or more in silicon dioxide, magnesium stearate, stearic acid, Pulvis Talci, hydrogenated vegetable oil or Polyethylene Glycol.
5. a preparation method for the arbitrary described metformin-glibenclamide capsule of claim 1-4, is characterized in that step is as follows:
(1) metformin hydrochloride, glibenclamide and filler pulverize and sieve;
(2) metformin hydrochloride, glibenclamide and the filler handled well is taken;
(3) load weighted metformin hydrochloride, glibenclamide and filler are joined wet granulator, after mix homogeneously, add binding agent and prepare soft material, granulate with screen cloth;
(4) material that step (3) obtains is added Fluidbedgranulatingdrier drying;
(5) material that step (4) obtains is added in pelletizing machine, use screen cloth granulate;
(6) material and lubricant that step (5) obtains is taken;
(7) material load weighted step (5) obtained and lubricant, join in mixer and mix;
(8) material of step (7) gained is added capsule filler and carry out capsule charge.
6. the preparation method of metformin-glibenclamide capsule according to claim 5, is characterized in that the order number of the sieve described in step (1) is 60-120 order.
7. the preparation method of metformin-glibenclamide capsule according to claim 5, is characterized in that the order number of the screen cloth described in step (3) is 14-30 order.
8. the preparation method of metformin-glibenclamide capsule according to claim 5, is characterized in that the order number of the screen cloth described in step (5) is 14-30 order.
9. the preparation method of metformin-glibenclamide capsule according to claim 5, is characterized in that the incorporation time described in step (7) is 5-30min.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106806644A (en) * | 2017-02-23 | 2017-06-09 | 王胜霞 | A kind of pharmaceutical composition and preparation method with reduction blood sugar recovery pancreas function |
| CN108836973A (en) * | 2018-08-28 | 2018-11-20 | 常州市阳光药业有限公司 | Metformin-glibenclamide capsule and preparation method thereof |
| CN110292569A (en) * | 2019-07-15 | 2019-10-01 | 广东人人康药业有限公司 | A kind of acetylcysteine capsules and preparation method thereof |
| CN113143940A (en) * | 2020-12-30 | 2021-07-23 | 成都恒瑞制药有限公司 | Preparation method of antidiabetic pharmaceutical composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5922769A (en) * | 1995-11-14 | 1999-07-13 | Abiogen Pharma S.R.L. | Glibenclamide-metformin combination for the treatment of diabetes mellitus of type II |
| CN1451385A (en) * | 2002-04-18 | 2003-10-29 | 谢理峰 | Oral compound hypoglycemic medicine |
| EP1435240A2 (en) * | 1998-07-15 | 2004-07-07 | Merck Sante | Solid oral dosage form comprising a combination of methformin and glibenclamide |
-
2015
- 2015-08-25 CN CN201510528094.4A patent/CN105030793A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5922769A (en) * | 1995-11-14 | 1999-07-13 | Abiogen Pharma S.R.L. | Glibenclamide-metformin combination for the treatment of diabetes mellitus of type II |
| EP1435240A2 (en) * | 1998-07-15 | 2004-07-07 | Merck Sante | Solid oral dosage form comprising a combination of methformin and glibenclamide |
| CN1451385A (en) * | 2002-04-18 | 2003-10-29 | 谢理峰 | Oral compound hypoglycemic medicine |
Non-Patent Citations (1)
| Title |
|---|
| 刘守信等: "用紫外分光光度法测定二甲双胍格列本脲胶囊中盐酸二甲双胍的含量", 《大连医科大学学报》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106806644A (en) * | 2017-02-23 | 2017-06-09 | 王胜霞 | A kind of pharmaceutical composition and preparation method with reduction blood sugar recovery pancreas function |
| CN108836973A (en) * | 2018-08-28 | 2018-11-20 | 常州市阳光药业有限公司 | Metformin-glibenclamide capsule and preparation method thereof |
| CN108836973B (en) * | 2018-08-28 | 2022-12-02 | 常州市阳光药业有限公司 | Metformin-glibenclamide capsule and preparation method thereof |
| CN110292569A (en) * | 2019-07-15 | 2019-10-01 | 广东人人康药业有限公司 | A kind of acetylcysteine capsules and preparation method thereof |
| CN110292569B (en) * | 2019-07-15 | 2021-11-02 | 广东人人康药业有限公司 | Acetylcysteine capsule and preparation method thereof |
| CN113143940A (en) * | 2020-12-30 | 2021-07-23 | 成都恒瑞制药有限公司 | Preparation method of antidiabetic pharmaceutical composition |
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Application publication date: 20151111 |