Influence of alkalizers on dissolution properties of telmisartan in solid dispersions prepared by cogrinding

作者：Lin Zhong, Xingyi Zhu, Bo Yu, Weike Su · 发表于：Drug Development and Industrial Pharmacy · 年份：2013 · DOI：10.3109/03639045.2013.841188 · 被引用次数：30 · 研究领域：Drug Solubulity and Delivery Systems、Phenothiazines and Benzothiazines Synthesis and Activities、Analytical Methods in Pharmaceuticals

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.