摘要
目的通过工艺参数优化,制备释放度符合肠溶制剂要求的盐酸二甲双胍肠溶微丸。方法使用流化床底喷包衣设备,首先制备并优化盐酸二甲双胍的载药微丸(黏合剂是HPMC,6×10-3Pa·s,用量为质量分数2.0%),然后考察肠溶包衣溶媒、HPMC隔离层和Eudragit?L 100-55用量对肠溶衣膜抗酸能力的影响。结果水分散体包衣法比乙醇溶液包衣法需要更多的包衣增重。隔离层可以显著降低水分散体包衣法所需的肠溶材料用量,但对于乙醇溶液包衣法制备的样品几乎没有影响结论当Eudragit?L 100-55包衣增重在25%以上时,以水分散体为包衣溶媒并增加隔离层的工艺方法,能使盐酸二甲双胍载药微丸具备较理想的肠溶特征。
Abstract
OBJECTIVE To develop enteric coated pellets containing metformin hydrochloride. METHODS Metformin hydrochloride loaded pellets were prepared using GPCG 1 fluid bed with the bottom spray processs, and metformin hydrochloride was layered on sugar pellets containing HPMC (6×10-3 Pa·s, 2.0%) as a binder. And Eudragit?L 100-55 or Eudragit?L 30D-55 were selected as enteric coated polymer of drug loaded pellets in the study. The influence of weight gain of polymers, coating medium and subcoat application on the dissolution properties of enteric coated metformin hydrochloride loaded pellets was investigated. RESULTS In order to pass the ChP enteric test, the aqueous and organic enteric coated pellets required 35% weight gain of Eudragit?L 30D-55 and 25% weight gain of Eudragit?L 100-55, respectively. The application of a subcoat of 3% weight gain of HPMC to the aqueous enteric coated pellets resulted in an evidently delay in metformin hydrochloride release in 0.1 mol·L-1 HCl, but it did not work in the organic enteric coated pellets. CONCLUSION When weight gain of Eudragit?L 30D-55 aqueous dispersions is above 25%, the metformin hydrochloride enteric pellets containing 3% weight gain of HPMC as subcoat can meet the ChP enteric claim.
关键词
盐酸二甲双胍 /
肠溶微丸 /
Eudragit?L30D-55 /
流化床
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Key words
metformin hydrochloride /
enteric pellets /
eudragit?L 30D-55
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高春生;单利;黄健;梅兴国.
盐酸二甲双胍肠溶微丸的成型工艺研究[J]. 中国药学杂志, 2006, 41(24): 1872-1875
GO Chun-sheng;SHN Li;HUNG Jin;MEI Xing-guo.
Development of Enteric Coated Metformin Hydrochloride Pellets [J]. Chinese Pharmaceutical Journal, 2006, 41(24): 1872-1875
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参考文献
[1] BALAN G，TIMMINS P，GREENE D S，et al. In vitro-in vivo correlation (IVIVC) models for metformin after administration of modified-release (MR) oral dosage forms to healthy human volunteers [J] . J Pharm Sci，2001，90(8)：1176-1185.
[2] STEPENSKY D，FRIEDMAN M，SROUR W，et al. Preclinical evaluation of pharmacokinetic pharmacodynamic rationale for oral CR metformin formulation[J] . J Controlled Release，2001，71：107-115.
[3] RAJU B，RESTA C，TIBALDI J T. Metformin and late gastrointestinal complications [J] . Am J Med，2000，109：260-261.
[4] HOFFMANA A，STEPENSKY D，LAVY E，et al. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms [J] . Int J Pharm，2004，277：141-153.
[5] YUEN K H，PEH K K，TAN B L. Relating in vitro/in vivo data of two controlled-release metformin formulations[J] . Drug Dev Ind Pharm，1999，25(5)：613-618.
[6] MULHBACHER J，SZABO P I，LENAERTS V. Cross-linked high amylose starch derivatives as matrices for controlled release of high drug loadings[J] . J Controlled Release，2001，76：51-58.
[7] COLO G D，FALCHI S，ZAMBITO Y. In vitro evaluation of a system for pH-controlled peroral delivery of metformin[J] . J Controlled Release，2002，80：119-128.
[8] FENG S H，WANG L P，WANG J F，et al. Determination of metformin hydrochloride enteric-coated tablets by UV[J] . Chin J Mod Appl Pharm（中国现代应用药学杂志），2001，18(6)：463-465.
[9] CHEN T，CHEN Q H. Study on pelletization technology of phenylpropanolamine hydrochloride [J] . Chin J Pharm（中国医药工业杂志），1999，30(8)：345-348.
[10] CHEN T，ZHANG Y，CHEN Q H. Studies on preparation of erythromycin enteric pellets by aqueous coating process [J] . Chin Pharm J（中国药学杂志），2002，37(6)：433-435.
[11] BRUCE L D，PETEREIT H U，BECKERT T，et al. Properties of enteric coated sodium valproate pellets [J] .Int J Pharm，2003，264：85-96.
[12] GARCIA A A，TORRADO S D，TORRADO J J. Comparative study of aqueous and organic enteric coatings of pheniramine maleate tablets [J] . Drug Dev Ind Pharm，1996，22：579-585.
[13] ZHANG G，SCHWARTZ J B，SCHNAARE R L. Bead coating. I. Change in release kinetics (and mechanism) due to coating levels[J] . Pharm Res，1991，8：331-335.
[14] DANGEL C，SCHEPKY G，REICH H B，et al. Comparative studies with kollicoat MAE 30 D and kollicoat MAE 30 DP in aqueous spray dispersions and enteric coatings on highly swellable caffeine cores[J] . Drug Dev Ind Pharm，2000，26：415-421.
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脚注
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