Kosto Timothy J, Nauman E Bruce
Howard P. Isermann Department of Chemical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
J Control Release. 2003 Dec 12;93(3):301-8. doi: 10.1016/j.jconrel.2003.08.018.
Polymer diffusion based on density-functional theory is applied to controlled release systems. These models explicitly treat the multiphase characteristics of biomolecule-polymer composites typical of drug delivery devices. Polymer diffusion was modeled using the modified Cahn-Hilliard equation with periodic boundary conditions in one dimension and near-zero concentration boundaries in the second dimension. The diffusional driving forces are differences in chemical potential based in part on the Flory-Huggins free energy of mixing in polymer systems rather than concentration gradients. Release rates from this model were compared to exponential models typically used in the drug delivery literature. Simulations based on this model showed that the diffusional exponent is 1/2; this exponent is consistent with Fickian models at early times. Particle growth, which also occurs in diffusing, dispersed systems, was observed. The particle growth exponent in these systems was 2/3, twice the value typical in bulk ripening systems. The increased growth rate was caused by the elimination of small particles due to diffusion out of the system, which removed the low particle size region of the distribution faster than ripening alone.
基于密度泛函理论的聚合物扩散被应用于控释系统。这些模型明确地处理了药物递送装置中典型的生物分子 - 聚合物复合材料的多相特征。聚合物扩散采用修正的Cahn - Hilliard方程进行建模，在一维上具有周期性边界条件，在二维上具有接近零浓度边界。扩散驱动力是化学势的差异，部分基于聚合物体系中弗洛里 - 哈金斯混合自由能而非浓度梯度。将该模型的释放速率与药物递送文献中通常使用的指数模型进行了比较。基于该模型的模拟表明，扩散指数为1/2；该指数在早期与菲克模型一致。观察到在扩散的分散体系中也会发生颗粒生长。这些体系中的颗粒生长指数为2/3，是本体熟化体系中典型值的两倍。生长速率的增加是由于小颗粒因扩散出系统而被消除，这比单独的熟化更快地去除了分布中的低粒径区域。
