Umer Muhammad Farooq, Stahl Valentin, Al-Gousous Jozef, Nawroth Thomas, Sun Wei-Jhe, Wu Fang, Jiang Wenlei, Gao Zongming, Langguth Peter
Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099 Mainz, Germany.
Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.
Pharmaceutics. 2025 Apr 25;17(5):567. doi: 10.3390/pharmaceutics17050567.
The food-induced viscosity of the media can alter tablet disintegration and eventually the release of the drug it contains. The extent of this retardation depends on tablet formulation factors, such as the solubility of its excipients. : This research aimed to study the effect of filler solubility on the disintegration and dissolution of tablets under different testing conditions. : Tablet formulations containing acetaminophen (as a model compound), mixtures of different ratios of fillers, and other excipients were directly compressed using uniform manufacturing parameters. These formulations were investigated under fasted- and fed-state conditions to determine the influence of viscosity on their disintegration, inspired by the liquid penetration ratio (LPR) theoretical framework. Disintegration and dissolution tests were performed using both compendial and novel testing apparatuses. : The soluble fillers in the tablets affected their disintegration and dissolution in the simulated fed-state medium, while fasted-state conditions affected the tablets only marginally. The testing devices showed partially contrasting results, which appeared to be due to the hydrodynamics of the testing media used. The novel CNC (computed numerical control) apparatus offered 3D motion and effectively exposed the tablets to the viscous testing media, unlike the compendial paddle apparatus. : This study explored the impact of filler solubility on the disintegration and dissolution of tablets. As the LPR framework revealed, fillers with a higher solubility have positive effects on the disintegration and dissolution of tablets in viscous conditions. Additionally, the proportion of soluble filler used is also inversely correlated with the disintegration time. Further investigation of the formulation parameters, as well as the testing conditions, would provide additional insights into the effects of food on these tablets.
食物引起的介质粘度会改变片剂的崩解，最终影响片剂中所含药物的释放。这种延缓的程度取决于片剂的配方因素，例如其辅料的溶解度。本研究旨在探讨在不同测试条件下，填充剂溶解度对片剂崩解和溶出的影响。含有对乙酰氨基酚（作为模型化合物）、不同比例填充剂混合物以及其他辅料的片剂配方，采用统一的生产参数直接压片。受液体渗透比（LPR）理论框架的启发，在禁食和进食状态下对这些配方进行研究，以确定粘度对其崩解的影响。使用药典规定的和新型测试仪器进行崩解和溶出试验。片剂中的可溶性填充剂会影响其在模拟进食状态介质中的崩解和溶出，而禁食状态对片剂的影响较小。测试装置显示出部分对比结果，这似乎是由于所用测试介质的流体动力学所致。与药典规定的桨式仪器不同，新型计算机数控（CNC）仪器提供三维运动，能有效地使片剂暴露于粘性测试介质中。本研究探讨了填充剂溶解度对片剂崩解和溶出的影响。正如LPR框架所揭示的，溶解度较高的填充剂对粘性条件下片剂的崩解和溶出有积极影响。此外，所用可溶性填充剂的比例也与崩解时间呈负相关。对配方参数以及测试条件的进一步研究，将为食物对这些片剂的影响提供更多见解。
