Ruiz-Picazo Alejandro, Jimenez Luis, Gonzalez-Alvarez Marta, Reinoso Oscar, Gonzalez-Alvarez Isabel, Bermejo Marival
Department Engineering Pharmacy Section, Miguel Hernandez University, San Juan de Alicante, 03550, Alicante, Spain.
Department of Systems Engineering and Automation, Systems Engineering and Automation Area, Miguel Hernandez University, Elche, 03202, Alicante, Spain.
AAPS J. 2025 Jul 22;27(5):121. doi: 10.1208/s12248-025-01110-0.
Gastric emptying plays a crucial role in the dissolution and absorption of oral drugs, particularly those with pH-dependent solubility, such as dipyridamole. This study evaluates the impact of gastric emptying kinetics on dipyridamole dissolution using a Gastrointestinal Simulator. A dynamic dissolution model incorporating first-order and Weibull kinetics was applied to simulate different gastric emptying profiles. Results indicate that dissolution behavior is significantly influenced by the rate and pattern of gastric emptying, affecting drug solubility and potential bioavailability. The Weibull model provided a more flexible fit to experimental data, but the external control shows that significant differences exist between theorical and experimental gastric volumes. These findings highlight the importance of integrating physiologically relevant gastric emptying models into biopharmaceutical assessments to improve the prediction of in vivo drug performance. This approach could enhance the design of oral formulations by optimizing dissolution profiles for weak base drugs.
胃排空在口服药物的溶解和吸收中起着关键作用,尤其是对于那些具有pH依赖性溶解度的药物,如双嘧达莫。本研究使用胃肠道模拟器评估胃排空动力学对双嘧达莫溶解的影响。应用结合一级动力学和威布尔动力学的动态溶解模型来模拟不同的胃排空曲线。结果表明,溶解行为受胃排空速率和模式的显著影响,进而影响药物溶解度和潜在生物利用度。威布尔模型对实验数据的拟合更灵活,但外部对照显示理论胃容积与实验胃容积之间存在显著差异。这些发现凸显了将生理相关的胃排空模型纳入生物药剂学评估以改善体内药物性能预测的重要性。这种方法可通过优化弱碱性药物的溶解曲线来改进口服制剂的设计。