Towards More Realistic In Vitro Release Measurement Techniques for Biodegradable Microparticles
Towards More Realistic In Vitro Release Measurement Techniques for Biodegradable Microparticles
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DOI：
10.1007/s11095-008-9747-4
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发表时间：
2009-03-01
影响因子：
3.7
通讯作者：
Siepmann, J.
中科院分区：
文献类型：
--
作者：
Klose, D.;Azaroual, N.;Siepmann, J.
目的。为了更好地了解环境条件对药物从可生物降解微颗粒中释放的重要性，从而开发更合适的体外释放测量技术。用核磁共振和紫外光谱分析表征了盐酸普萘洛尔在各种琼脂糖凝胶中的扩散。用菲克定律对质量传递动力学进行了理论预测。将这种琼脂糖凝胶中基于plga的微颗粒的药物释放量与在搅拌散装液体中测量的药物释放量进行了比较（“标准”方法）。核磁共振分析显示，尽管系统的力学性能存在显著差异，但药物扩散率几乎与水凝胶浓度无关。这是由于药物分子/离子相对于水凝胶网尺寸较小。有趣的是，理论上预测的药物浓度-距离分布可以通过独立的实验来证实。最重要的是，从实际的角度来看，从同一批基于plga的微颗粒到搅拌良好的散装流体和半固体琼脂糖凝胶的释放速度有显著差异。在确定生物可降解微粒的药物释放测量的体外条件时，必须非常小心。获得的新见解可以帮助促进更合适的体外释放测试程序的发展。
Purpose. To better understand the importance of the environmental conditions for drug release from biodegradable microparticles allowing for the development of more appropriate in vitro release measurement techniques.Methods. Propranolol HCl diffusion in various agarose gels was characterized by NMR and UVanalysis. Fick's law was used to theoretically predict the mass transport kinetics. Drug release from PLGA-based microparticles in such agarose gels was compared to that measured in agitated bulk fluids ("standard" method).Results. NMR analysis revealed that the drug diffusivity was almost independent of the hydrogel concentration, despite of the significant differences in the systems' mechanical properties. This is due to the small size of the drug molecules/ions with respect to the hydrogel mesh size. Interestingly, the theoretically predicted drug concentration-distance-profiles could be confirmed by independent experiments. Most important from a practical point of view, significant differences in the release rates from the same batch of PLGA-based microparticles into a well agitated bulk fluid versus a semi-solid agarose gel were observed.Conclusion. Great care must be taken when defining the in vitro conditions for drug release measurements from biodegradable microparticles. The obtained new insight can help facilitating the development of more appropriate in vitro release testing procedures.