The present study is focused on the development of methodology for testing drug sensitivity to hydrolytic degradation in different pH conditions in solid-state. To test hydrolytic degradations in solid-state, methodology using different silica and silicates with varying pH (3.9–9.7) was developed. Hydrolytic degradations in varying pH conditions of two drugs, bisoprolol and sofosbuvir were examined in solution as well as in solid-state using HPLC. Impurity profiles in solid-state and in solution differed for sofosbuvir. A bisoprolol hydrolytic curve measured in solid-state showed different dependence between pH and degradation than in solution. The main difference between testing the effects of pH on API stability in solution and in solid-state is that different degradation mechanisms are taking place. It was confirmed that degradation mechanisms observed in solid-state testing are much closer to degradation mechanisms observed for solid dosage forms than degradation mechanism observed while using standard method of testing in solution.

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中文翻译：

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研究 API 对固态不同 pH 条件下水解降解敏感性的方法学

本研究的重点是开发测试药物在不同 pH 条件下对固态水解降解的敏感性的方法。为了测试固态中的水解降解，开发了使用不同 pH 值 (3.9-9.7) 的不同二氧化硅和硅酸盐的方法。两种药物比索洛尔和索非布韦在不同 pH 条件下的水解降解在溶液中以及使用 HPLC 进行了固态检测。固态和溶液中的杂质分布对于索非布韦是不同的。在固态下测量的比索洛尔水解曲线显示出与在溶液中不同的 pH 值和降解之间的依赖性。测试 pH 值对 API 在溶液中和固态中稳定性的影响的主要区别在于发生了不同的降解机制。

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