普伐他汀在模拟体内酸碱环境中的稳定性

Study on stability of pravastatin under simulated in vivo conditions

目的:研究普伐他汀在模拟体内酸碱环境中的稳定性。方法:采用高效液相色谱法测定在不同pH溶液中普伐他汀的剩余浓度和生成3’α-异普伐他汀的浓度,考察普伐他汀的转化情况,并数学拟合求解转化动力学方程。结果:普伐他汀在模拟体内胃液的酸性条件下不稳定,易发生转化,尤其在模拟体内空腹时胃液的酸性条件下转化迅速,其初期的转化速率符合一级动力学;3’α-异普伐他汀为普伐他汀的一个主要转化产物,其生成的最适pH值是2;普伐他汀在模拟体内肠道环境的条件下较稳定,不发生明显转化。结论:普伐他汀在酸性条件下的转化应引起重视。因此为降低普伐他汀在胃中的转化,提高其生物利用度,应采用多种制剂手段。

OBJECTIVE The stability of pravastatin under simulated in vivo conditions was studied. METHODS Residule concentrations of pravastatin and concentrations of 3＇ α-isopravastatin in different pH solutions were determined by HPLC, which deduced the transformation kinetics functions, RESULTS The results showed that pravastatin was unstable under the silnulated stomach conditions it transformed rapidly especially in gastric juice under fasted conditions. Initial transformation of pravastatin displayed first-order kinetics. Pravastatin was mainly transformed to 3＇ α-isopravastatin, The optimal pH value for the transformation was 2, Pravastatin was stable under the conditions of simulated the intestine pH and no transformation was found. CONCLUSION Attention should be paid to the transformation of pravastatin to 3＇ α-isopravastatin under aqueous acid conditions. Therefore several formulation strategies should be applied in order to reduce the transformation of pravastatin in the stomach and improve its bioavailability.