The computer program ASAPprime® has been used successfully for some time to predict the stability of active pharmaceutical ingredients (APIs) in solid-dosage forms. In this study, we have demonstrated that the ASAPprime® program can also be used to predict the slow-down in dissolution of two APIs in an immediate release tablet. The tablets were pre-equilibrated at 25 °C at different relative humidities (30–75 %), sealed in aluminum pouches and stored at temperatures ranging from 50–60 °C for 3, 7 or 14 days. The storage times were selected to encompass the time needed to produce a slowdown in dissolution such that the amount of the two APIs fell below the acceptance criteria of no less than 80 % dissolved in 20 min. Up to 6 months of stability data from a 40 °C/75%RH open dish study were also included in the modeling. The effects of temperature (T in °K) and relative humidity (RH) were then shown to be related to the isoconversion (IC) time by an empirical, modified Arrhenius equations, where IC is the time for the amount dissolved to equal 80 % of the label claim. These studies showed that while the slowdown in dissolution of API 2 was influenced more by the relative humidity than API 1, the overall slowdown in dissolution was more sensitive to changes in temperature than changes in relative humidity. In addition to showing that ASAPprime® could be used to model the effects of temperature and relative humidity on dissolution, the software was also used to demonstrate that no special precautions were necessary to protect the tablets from moisture and they could be stored in Aclar blisters®. It was also shown that the water content of the tablet was not a critical quality attribute and need not be included in the drug product specification.

中文翻译：

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从使用的加速稳定性评估方案（ASAP含有两种活性药物成分的速释片的药物溶出的变化预测素®）

计算机程序ASAPprime®已成功使用了一段时间来预测固体剂型形式的活性药物成分（API）的稳定性。在这项研究中，我们证明了ASAPprime®程序还可用于预测速释片剂中两种API的溶出度降低。将片剂在25°C的不同相对湿度（30–75％）下预先平衡，密封在铝袋中，并在50–60°C的温度下保存3、7或14天。选择储存时间以涵盖溶解速度减慢所需的时间，以使两种API的量降至20分钟内溶解不少于80％的可接受标准以下。建模中还包括来自40°C / 75％RH开盘研究的长达6个月的稳定性数据。然后，通过经验修正的Arrhenius方程，证明温度（T以°K为单位）和相对湿度（RH）的影响与等转化（IC）时间有关，其中IC是溶解量等于80％的时间标签声明。这些研究表明，尽管相对湿度比API 1对API 2溶解的减慢影响更大，但总溶解度对温度的变化比相对湿度的变化更敏感。除了表明ASAPprime®可用于模拟温度和相对湿度对溶出度的影响外，该软件还用于证明不需要采取特殊的预防措施来保护片剂免受潮气的影响，并且可以将其存储在Aclarblisters®中。