Zentiva, k.s., Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic; Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic.
Zentiva, k.s., Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic; Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic.
J Pharm Biomed Anal. 2023 Aug 5;232:115417. doi: 10.1016/j.jpba.2023.115417. Epub 2023 Apr 23.
A new approach for testing drug sensitivity to autooxidative degradation in the solid state is demonstrated in this work. A novel solid-state form of stressing agent for autooxidation has been proposed, based on azobisisobutyronitrile loaded into mesoporous silica carrier particles. The new solid-state form of the stressing agent was applied in degradation studies of two active pharmaceutical ingredients: bisoprolol and abiraterone acetate. The effectiveness and predictivity of the method were evaluated by comparing impurity profiles with those obtained by traditional stability testing of commercial tablets containing the investigated APIs. The results obtained by the new solid-state stressor were also compared with those obtained by an existing method for testing peroxide oxidative degradation in the solid state using a complex of polyvinylpyrrolidone with hydrogen peroxide. It was found that the new silica particle-based stressor was able to effectively predict which impurities could be formed by autooxidation in tablets and that this new approach is complementary to methods for testing peroxide oxidative degradation known from the literature.
本工作展示了一种用于测试固体状态下药物自动氧化降解敏感性的新方法。基于负载在介孔硅载体颗粒中的偶氮二异丁腈，提出了一种用于自动氧化的新型固态促氧化剂形式。新的固态促氧化剂形式应用于两种活性药物成分的降解研究：比索洛尔和醋酸阿比特龙。通过将该方法获得的杂质谱与含有所研究 API 的市售片剂的传统稳定性测试获得的杂质谱进行比较，评估了该方法的有效性和可预测性。还将新的固态应力剂的结果与使用聚乙烯吡咯烷酮与过氧化氢的复合物在固态中测试过氧化物氧化降解的现有方法的结果进行了比较。结果发现，基于新的硅胶颗粒的应力剂能够有效地预测片剂中可能通过自动氧化形成的杂质，并且这种新方法与文献中已知的过氧化物氧化降解测试方法是互补的。
