Zhong Lin, Zhu Xingyi, Yu Bo, Su Weike
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology , Hangzhou , PR China.
Drug Dev Ind Pharm. 2014 Dec;40(12):1660-9. doi: 10.3109/03639045.2013.841188. Epub 2013 Oct 7.
The amorphous solid dispersions of telmisartan salts were prepared by cogrinding, in presence of alkalizers and polyvinylpyrrolidone (PVPk30). Five alkalizers in this study were MgO, Na2CO3, K2CO3, NaHCO3 and meglumine. In soft mode using a roll mill, the drug could not form salt with MgO or NaHCO3, whereas partial drug had been transformed into salt with carbonates or meglumine. Under cogrinding, the organic base meglumine was easier to react with telmisartan than other two carbonates. For getting good dissolution performance, the drug had to be transformed into salt completely. A high intensity oscillating mill was applied for producing telmisartan meglumine salt. Multi-instrumental characterizations attested the formation of amorphous salt by high mechanical process, involving dissolution test, fourier transform infrared spectroscopy and powder X-ray diffractometry. It was evident that solid dispersions of telmisartan meglumine salt significantly increased the drug dissolution rate in intestinal fluid.
在碱化剂和聚乙烯吡咯烷酮（PVPk30）存在的情况下，通过共研磨制备替米沙坦盐的无定形固体分散体。本研究中的五种碱化剂为氧化镁、碳酸钠、碳酸钾、碳酸氢钠和葡甲胺。在使用辊磨机的软模式下，药物不能与氧化镁或碳酸氢钠形成盐，而部分药物已与碳酸盐或葡甲胺转化为盐。在共研磨过程中，有机碱葡甲胺比其他两种碳酸盐更容易与替米沙坦反应。为了获得良好的溶解性能，药物必须完全转化为盐。采用高强度振荡磨制备替米沙坦葡甲胺盐。多仪器表征证实了通过高机械过程形成无定形盐，包括溶出度试验、傅里叶变换红外光谱和粉末X射线衍射法。显然，替米沙坦葡甲胺盐的固体分散体显著提高了药物在肠液中的溶解速率。
