CN1294908C - 口服格列齐特缓释制剂 - Google Patents
口服格列齐特缓释制剂 Download PDFInfo
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- CN1294908C CN1294908C CNB031350984A CN03135098A CN1294908C CN 1294908 C CN1294908 C CN 1294908C CN B031350984 A CNB031350984 A CN B031350984A CN 03135098 A CN03135098 A CN 03135098A CN 1294908 C CN1294908 C CN 1294908C
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- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 title claims abstract description 23
- 229960000346 gliclazide Drugs 0.000 title claims abstract description 23
- 239000000203 mixture Substances 0.000 title description 6
- 238000009472 formulation Methods 0.000 title description 5
- 238000013265 extended release Methods 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 239000003085 diluting agent Substances 0.000 claims abstract description 7
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- 239000003405 delayed action preparation Substances 0.000 claims abstract 6
- 239000011159 matrix material Substances 0.000 claims abstract 3
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- 239000000463 material Substances 0.000 claims description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- 239000004203 carnauba wax Substances 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 235000013871 bee wax Nutrition 0.000 claims 1
- 239000012166 beeswax Substances 0.000 claims 1
- 235000013869 carnauba wax Nutrition 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 235000021003 saturated fats Nutrition 0.000 abstract description 3
- 239000012738 dissolution medium Substances 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000003111 delayed effect Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000007766 cera flava Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011978 dissolution method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007962 solid dispersion Substances 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229940061158 gliclazide 30 mg Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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Abstract
一种口服格列齐特缓释制剂，包括有效成分格列齐特以及稀释剂、润滑剂和助流剂，其特征在于该缓释制剂中含有生物溶蚀性骨架材料，该骨架材料由至少一种蜡类或饱和脂肪类所构成。为更好地控制缓释释放，制剂中还可以加入表面活性剂。本制剂在4-6小时内释放格列齐特总量的50%，而且不受溶解介质pH值的影响。
Description
技术领域
本发明涉及一种口服药物制剂，确切地说是一种含有生物溶蚀性骨架的口服格列齐特缓释制剂。
背景技术
格列齐特为第二代磺酰脲类降糖药(又名甲磺吡脲)，是临床常用的降血糖药，由于其疗效确切，被列入国家基本药物目录和医疗保险用药。目前临床使用的为每片含80mg剂量的口服普通片，常规的平均处方量是每天给药二次，每次一片，有时也视糖尿病的严重性，每天给药1-4片，分几次给药。这种口服普通片释放迅速，有效成分在患者血液中短期高浓度(峰值)，而缓释制剂可避免这样的峰值，使有效成分在患者血液中的浓度均衡和稳定，从而避免峰值引起的副作用。
CN1342068A公开了一种口服缓释骨架片，为亲水性骨架，包括至少一种纤维素聚合化合物和葡萄糖浆。
发明内容
本发明所提供的口服格列齐特缓释制剂，包括有效成分格列齐特以及稀释剂、润滑剂和助流剂，其特征在于：该缓释制剂中含有生物溶蚀性骨架材料，所述的生物溶蚀性骨架材料由至少一种蜡类或者饱和脂肪类所构成。
所述的蜡类为蜂蜡或合成蜡或巴西棕榈蜡等。
所述的饱和脂肪类为硬脂肪酸或氢化植物油等。
生物溶蚀性骨架材料占制剂总重量的10％-40％，以15％-25％为佳。
有效成分格列齐特占制剂总重量的7.5％-25％。为更好地控制格列齐特缓释释放，该缓释制剂中还可以加入表面活性剂，为十二烷基硫酸钠或吐温类等。表面活性剂占制剂总重量的5％-10％。
所述的稀释剂采用已知的磷酸盐或酸式磷酸盐或者碳酸盐或酸式碳酸盐，优选碳酸氢钠。稀释剂占制剂总重量的20％-70％，以45％-65％为佳。
所述的润滑剂采用已知的硬脂酸或其盐，优选硬脂酸镁。
所述的助流剂选用已知的二氧化硅。
本发明所提供的口服格列齐特缓释制剂采用已知的凝固法制备。这就是首先将格列齐特、稀释剂、表面活性剂混合，然后将混合物加入已加热熔融的生物溶蚀性骨架材料中，搅拌混匀，冷却、粉碎、过筛，然后加入润滑剂、助流剂，混匀，压片或灌制胶囊即可。
本发明所提供的口服格列齐特缓释制剂，采用生物溶蚀性骨架材料与表面活性剂和弱碱性的稀释剂进行组合，其体外释放符合要求。格列齐特在4-6小时之间释放总量的50％，而且不受PH值的影响(见附图)。
附图说明：
附图所示是格列齐特在不同PH值的溶解介质中的释放曲线，附图1为PH6.8的溶解介质，附图2为PH7.8的溶解介质。
曲线所示格列齐特的缓释不受PH值的影响。
具体实施方式
现以制备1000片，每片含格列齐特30mg为例，非限定实施例叙述如下
例1、
格列齐特 30g
碳酸氢钠 130g
蜂蜡 35g
吐温80 15g
硬脂酸镁 2g
二氧化硅 1g
制法：将蜂蜡于混合器中，置水浴上加热熔融，加入预混合的格列齐特、碳酸氢钠、吐温80，于半固态搅拌混匀，边搅拌，边冷却，制成固体分散体，粉碎过40-60目筛，用50％乙醇制成颗粒，烘干后加入润滑剂、助流剂，混匀，压1000片或灌装1000粒胶囊即可。
所制片剂(或胶囊)照释放度测定法《中国药典2000版二部附录XD第一法》，采用溶出度测定法第一法装置，以pH6.8和pH7.8的磷酸盐缓冲液1000ml为介质，转速100转/分钟；测定数据见下表
释放度测定数据(％)
| 1h | 2h | 4h | 8h | 12h | ||
| 实施例1 | PH6.8 | 26 | 38 | 62 | 88 | 101 |
| PH7.8 | 27 | 39 | 65 | 90 | 100 |
例2-例6：
氢化植物油于混合器中，置水浴上加热熔融，加入预混合的格列齐特、碳酸氢钠、十二烷基硫酸钠，于半固态搅拌混匀，边搅拌、边冷却，制成固体分散体于摇摆颗粒机中过20-24目筛，加入硬脂酸镁和二氧化硅混匀，8mm平冲压片1000片或灌1000颗胶囊。
例2-例6所制片剂(或胶囊)照释放度测定法《中国药典2000版二部附录XD第一法》，采用溶出度测定法第一法装置，以pH6.8和pH7.8的磷酸盐缓冲液1000ml为介质，转速100转/分钟；测定数据见下表
释放度测定数据(％)
Claims (3)
1、一种口服格列齐特缓释制剂，包括有效成分格列齐特、稀释剂、润滑剂和助流剂，其特征在于：该缓释剂中含有蜂蜡或合成蜡或巴西棕榈蜡或氢化植物油中至少一种生物溶蚀性骨架材料，生物溶蚀性骨架材料占制剂总重量的10％～40％。
2、根据权利要求1所述的缓释制剂，其特征在于：生物溶蚀性骨架材料占制剂总重量的15％～25％。
3、根据权利要求1或2所述的缓释制剂，其特征在于：该缓释制剂中含有表面活性剂十二烷基硫酸钠或吐温，表面活性剂占制剂总重量的5％～10％。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031350984A CN1294908C (zh) | 2003-06-08 | 2003-09-28 | 口服格列齐特缓释制剂 |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN03131849.5 | 2003-06-08 | ||
| CN03131849 | 2003-06-08 | ||
| CNB031350984A CN1294908C (zh) | 2003-06-08 | 2003-09-28 | 口服格列齐特缓释制剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1572294A CN1572294A (zh) | 2005-02-02 |
| CN1294908C true CN1294908C (zh) | 2007-01-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB031350984A Expired - Fee Related CN1294908C (zh) | 2003-06-08 | 2003-09-28 | 口服格列齐特缓释制剂 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2928836B1 (fr) * | 2008-03-21 | 2011-08-26 | Servier Lab | Forme galenique secable permettant une liberation modifiee du principe actif |
| CN101721392B (zh) * | 2008-10-24 | 2012-02-08 | 天津市铭泰医药科技有限公司 | 一种格列齐特缓释胶囊的制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6056977A (en) * | 1997-10-15 | 2000-05-02 | Edward Mendell Co., Inc. | Once-a-day controlled release sulfonylurea formulation |
| CN1342068A (zh) * | 1999-02-01 | 2002-03-27 | 阿迪尔公司 | 在口服途径给药之后延长释放甲磺吡脲的骨架片 |
| WO2002074285A1 (en) * | 2001-03-16 | 2002-09-26 | Andrx Corporation | Controlled release sulfonylurea formulation |
-
2003
- 2003-09-28 CN CNB031350984A patent/CN1294908C/zh not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6056977A (en) * | 1997-10-15 | 2000-05-02 | Edward Mendell Co., Inc. | Once-a-day controlled release sulfonylurea formulation |
| CN1342068A (zh) * | 1999-02-01 | 2002-03-27 | 阿迪尔公司 | 在口服途径给药之后延长释放甲磺吡脲的骨架片 |
| WO2002074285A1 (en) * | 2001-03-16 | 2002-09-26 | Andrx Corporation | Controlled release sulfonylurea formulation |
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| Publication number | Publication date |
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| CN1572294A (zh) | 2005-02-02 |
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