Klose D, Azaroual N, Siepmann F, Vermeersch G, Siepmann J
College of Pharmacy, JE 2491, University of Lille, 3 rue du Professeur Laguesse, 59006, Lille, France.
Pharm Res. 2009 Mar;26(3):691-9. doi: 10.1007/s11095-008-9747-4. Epub 2008 Oct 29.
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.
Propranolol HCl diffusion in various agarose gels was characterized by NMR and UV analysis. 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).
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.
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.
为了更好地理解环境条件对可生物降解微粒药物释放的重要性，从而开发更合适的体外释放测量技术。
通过核磁共振（NMR）和紫外（UV）分析对盐酸普萘洛尔在各种琼脂糖凝胶中的扩散进行表征。利用菲克定律从理论上预测传质动力学。将基于聚乳酸-羟基乙酸共聚物（PLGA）的微粒在这种琼脂糖凝胶中的药物释放与在搅拌的大量流体中测量的结果（“标准”方法）进行比较。
核磁共振分析表明，尽管体系的机械性能存在显著差异，但药物扩散系数几乎与水凝胶浓度无关。这是由于相对于水凝胶网孔尺寸，药物分子/离子尺寸较小。有趣的是，理论预测的药物浓度-距离曲线可以通过独立实验得到证实。从实际角度来看，最重要的是，观察到同一批基于PLGA的微粒在充分搅拌的大量流体与半固体琼脂糖凝胶中的释放速率存在显著差异。
在确定可生物降解微粒药物释放的体外条件时必须格外小心。所获得的新见解有助于推动开发更合适的体外释放测试程序。
