Waterman Kenneth C, Chen Lili, Waterman Philip, MacDonald Bruce C, Monahan Andrew P, Scrivens Garry
a FreeThink Technologies, Inc. , Branford , CT , USA ;
b Pfizer Inc. , Groton , CT , USA ;
Drug Dev Ind Pharm. 2016 Oct;42(10):1571-8. doi: 10.3109/03639045.2016.1153648. Epub 2016 Apr 6.
A model is presented for determining the time when an active pharmaceutical ingredient in tablets/powders will remain within its specification limits during an in-use period; that is, when a heat-induction sealed bottle is opened for fixed time periods and where tablets are removed at fixed time points. This model combines the Accelerated Stability Assessment Program to determine the impact on degradation rates of relative humidity (RH) with calculations of the RH as a function of time for the dosage forms under in-use conditions. These calculations, in a conservative approach, assume that the air inside bottles with broached heat-induction seals completely exchanges with the external environment during periods when the bottle remains open. The solid dosages are assumed to sorb water at estimable rates during these openings. When bottles are capped, the moisture vapor transmission rate can be estimated to determine the changing RH inside the bottles between opening events. The impact of silica gel desiccants can also be included in the modeling.
提出了一种模型，用于确定片剂/散剂中的活性药物成分在使用期内何时将保持在其规格限度内；也就是说，当热感应密封瓶在固定时间段打开且在固定时间点取出片剂时。该模型将加速稳定性评估程序结合起来，以确定相对湿度（RH）对降解速率的影响，并结合了使用条件下剂型的RH随时间变化的计算。在保守方法中，这些计算假设带有开口热感应密封的瓶内空气在瓶子保持打开的时间段内与外部环境完全交换。假设在这些打开期间，固体剂型以可估计的速率吸收水分。当瓶子加盖时，可以估计水分透过率以确定两次打开事件之间瓶内RH的变化。硅胶干燥剂的影响也可纳入建模。
