影响奥美沙坦酯片溶出度的关键工艺参数考察  

Investigation on Influences of Critical Process Parameters of Olmesartan Medoxomil Tablets on Dissolution

作　　者：严相平[1] 周方泰 谢浩[1] 

机构地区：[1]南京工业大学江苏省药物研究所,江苏南京210009 [2]南京工业大学药学院,江苏南京210009

出　　处：《中国医药工业杂志》2016年第11期1414-1417,共4页Chinese Journal of Pharmaceuticals

摘　　要：考察了奥美沙坦酯在水、0.1 mol/L盐酸、pH 4.5乙酸盐缓冲液和pH 6.8磷酸盐缓冲液中的饱和溶解度,确定在pH 6.8介质中能满足漏槽条件。采用正交试验考察了奥美沙坦酯片处方工艺中乳糖与微晶纤维素比例、黏合剂浓度、压片压力和原料药粒径对片剂在pH 6.8介质中溶出度的影响。结果显示,原料粒径对溶出度的影响最关键,需控制粒径d(0.9)、d(0.5)和d(0.1)小于10.0、3.5、0.6mm。并且,包衣(增重约2.8%)前后,片剂的溶出行为无明显变化。小试和中试产品在上述4种介质中的溶出曲线与原研制剂(傲坦)相似。The saturated solubility values of olmesartan medoxomil in water, 0.1 mol/L hydrochloric acid, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were determined. The results showed that the pH 6.8 phosphate buffer could provide sink conditions. The influences of lactose to microcrystalline cellulose ratio, concentration of adhesive solution, tableting pressure and particle size of bulk drug on the dissolution of the self-made olmesartan medoxomil tablets in pH 6.8 medium were investigated by orthogonal design, and the factor ＂particle size of bulk drug＂ was confirmed as the most critical process parameter. The results showed that the values of d（0.9）, d（0.5） and d（0.1） should be controlled less than 10.0, 3.5 and 0.6 μm. Furthermore, the dissolution profiles of the self-made tablets before and after coating with coating level of about 2.8 % had no significant changes. The dissolution profiles of small- and polite-scale tablets were all similar to the profile of reference listed drug product （Olmetec） in above four media.

关 键 词：奥美沙坦酯 片剂 原料药粒径 溶出度 相似性评价 

分 类 号：R944.4[医药卫生—药剂学]