Division of Pharmaceutical Analysis, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, St. Louis, Missouri 63110.
Division of Pharmaceutical Analysis, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, St. Louis, Missouri 63110.
J Pharm Sci. 2019 Mar;108(3):1189-1194. doi: 10.1016/j.xphs.2018.10.014. Epub 2018 Oct 19.
In contrast to nifedipine matrix-based extended-release dosage forms, the osmotic pump drug delivery systems have a zero-order drug release independent of external variables such as pH, agitation rate, and dissolution media. The objective of this study focuses on the in vitro evaluation of the mechanical properties of osmotic pump and polymer matrix-based formulations in dissolution media, and the potential impacts that media pH and simulated gastrointestinal contraction have on drug release. Two strengths of osmotic pump product A and polymer matrix-based product B were used in this study. An in-house system was developed with the capability of applying mechanical compression and monitoring mechanical properties of sample during dissolution testing. A United States Pharmacopeia or an in-house apparatus was used for dissolution testing under various conditions. Compared to the product A, the mechanical properties of the product B change significantly at various pHs and mechanical compressions. The results suggest that polymer matrix-based products bear a risk of formulation-related interactions with the gastrointestinal tract during in vivo drug dissolution, especially in the case of concomitant pH and gastric contractile changes. Modified dissolution testing devices may help formulation scientists in product development and provide regulatory agencies with an additional metric for quality assurance of drug products.
与硝苯地平基质型控释制剂不同，渗透泵药物递送系统具有零级药物释放，不受 pH、搅拌速度和溶解介质等外部变量的影响。本研究的目的是在溶解介质中评估渗透泵和聚合物基质型制剂的机械性能，以及介质 pH 和模拟胃肠道收缩对药物释放的潜在影响。本研究使用了两种强度的渗透泵产品 A 和聚合物基质型产品 B。开发了一种内部系统，具有在溶解测试过程中施加机械压缩和监测样品机械性能的能力。使用美国药典或内部设备在各种条件下进行溶解测试。与产品 A 相比，产品 B 的机械性能在不同 pH 值和机械压缩下变化显著。结果表明，聚合物基质型产品在体内药物溶解过程中与胃肠道发生配方相关相互作用的风险较高，尤其是在 pH 值和胃收缩同时发生变化的情况下。改良的溶解测试设备可能有助于制剂科学家进行产品开发，并为监管机构提供药物产品质量保证的附加指标。
