National Institute of Chemistry, Ljubljana, Slovenia.
J Control Release. 2011 Nov 7;155(3):409-17. doi: 10.1016/j.jconrel.2011.06.038. Epub 2011 Jul 3.
Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes.
基于经过精心设计的实验结果，我们进行了适当的理论建模，为药物-基质相互作用显著影响介孔材料的释放曲线提供了明确的证据。在实验曲线上，这些相互作用表现为长时间不收敛和释放动力学与孔径的反比关系。在非相互作用系统中，这些现象都不应出现。尽管这两种现象在以前的研究中已经被零星地观察到，但它们并没有用一般和一致的理论模型来解释。该概念以吲哚美辛嵌入 SBA-15 和 MCM-41 多孔硅酸盐的模型药物为例进行了演示。在药物与壁面之间存在显著吸引力的情况下，实验释放曲线与理论预测非常吻合。后者使用二维福克-普朗克方程进行描述。可以说，相互作用影响了局部通量具有非零轴向分量的孔的相对横截面，从而控制了药物向体相溶液的有效传递。最后，我们确定了决定释放动力学孔径依赖性的关键参数，并构建了各种不同输运状态的动态相图。
