Almukainzi May, Okumu Arthur, Wei Hai, Löbenberg Raimar
Faculty of Pharmacy & Pharmaceutical Science, 3-142K Katz Group Centre for Pharmacy & Health Research, University of Alberta, 11361 - 87 Ave., Edmonton, AB, T6G 2E1, Canada.
AAPS PharmSciTech. 2015 Feb;16(1):217-21. doi: 10.1208/s12249-014-0241-5. Epub 2014 Nov 20.
Dissolution testing is a performance test for many dosage forms including tablets and capsules. The objective of this study was to evaluate if computer simulations can predict the in vitro dissolution of two model drugs for which different dissolution data were available. Published montelukast sodium and glyburide dissolution data was used for the simulations. Different pharmacopeial and biorelevant buffers, volumes, and rotations speeds were evaluated. Additionally, a pH change protocol was evaluated using these buffers. DDDPlus™ 3, Beta version (Simulation Plus, Inc.), was used to simulate the in vitro dissolution data. The simulated data were compared with the in vitro data. A regression coefficient between predicted and observed data was used to assess the simulations. The statistical analysis of Montelukast sodium showed that there was a significant correlation between the in vitro release data and the predicted data for all cases except for one buffer. For glyburide, there was also a significant correlation between the experimental data and the predicted data using single pH conditions. Using the dynamic pH protocol, a correlation was significant for one biorelevant media. The simulations showed that both in vitro drug releases were sensitive to solubility effects which confirmed their BCS class II category. Computer simulations of the in vitro release using DDDPlus™ have the potential to estimate the in vivo dissolution at an early stage in the drug development process. This might be used to choose the most appropriate dissolution condition to establish IVIVC and to develop biorelevant in vitro performance tests to capture critical product attributes for quality control procedures in quality by design environments.
溶出度测试是包括片剂和胶囊在内的许多剂型的性能测试。本研究的目的是评估计算机模拟是否能够预测两种有不同溶出数据的模型药物的体外溶出情况。已发表的孟鲁司特钠和格列本脲的溶出数据用于模拟。评估了不同的药典缓冲液和生物相关缓冲液、体积及转速。此外，还使用这些缓冲液评估了pH变化方案。使用DDDPlus™ 3 Beta版本（Simulation Plus公司）模拟体外溶出数据。将模拟数据与体外数据进行比较。用预测数据与实测数据之间的回归系数评估模拟结果。孟鲁司特钠的统计分析表明，除一种缓冲液外，在所有情况下体外释放数据与预测数据之间均存在显著相关性。对于格列本脲，在单一pH条件下实验数据与预测数据之间也存在显著相关性。使用动态pH方案时，在一种生物相关介质中相关性显著。模拟结果表明，两种药物的体外释放均对溶解度效应敏感，这证实了它们的BCS II类属性。使用DDDPlus™对体外释放进行计算机模拟有潜力在药物开发过程的早期阶段估计体内溶出情况。这可用于选择最合适的溶出条件以建立体外-体内相关性，并开发生物相关的体外性能测试，以捕捉质量源于设计环境中质量控制程序的关键产品属性。
