溶胀壳聚糖膜药物扩散的数学研究

Alexey O. Syromyasov, A. Shurshina, Dmitry V. Galkin
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引用次数: 0

摘要

现代剂型之一是药物饱和的有机薄膜:将这种薄膜涂在皮肤上后,药物释放,从而提供愈合效果。本文主要研究了壳聚糖和氨基苄胺或头孢唑啉的薄膜。这种膜最重要的特性是用扩散系数来描述药物的释放速度。为了找到它,将薄膜置于水中,并在不同的时刻测量薄膜中的平均药物浓度。这里出现了两个问题。首先,薄膜的性质会因为膨胀而改变。其次,扩散并不是发生在胶片内部的唯一过程。为了处理这些影响,作者假设扩散系数是时变的,用描述药物分子脱离高分子基质的ODE来完成数学模型。模型中所有方程均可解析求解,因此膜内平均药物浓度是已知的时间函数。因此,用最小二乘框架求解已知函数的未知标量参数就足够了。求解过程中出现的表达式比较复杂,因此优选非梯度法进行优化。将所描述的方法应用于实验数据,可以得到较好的准确性,并且结果可以从物理化学的角度进行解释。特别是薄膜膨胀不影响释放速率。事实上,实验前几个小时的扩散速率较大,药物的主要部分在肿胀开始前就释放了,起着重要的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mathematical study of medicine diffusion from swelling chitosan film
One of modern dosage forms is a medicine-saturated organic film: after putting this film onto a skin the medicine releases thus providing healing effect. Present article concerns films based on chitosan and containing amikacinum or cefazolinum. The most important characteristic of such film is rate of medicine release described by diffusion coefficient. To find it the film is placed in water and the average medicine concentration in the film is measured at different time moments. Two problems arise here. First, the film properties change because of its swelling. Second, diffusion is not the only process that takes place inside the film. To deal with these effects, authors suppose diffusion coefficient to be time-variable and complete the mathematical model with ODE describing detachment of medicine molecules from high-molecular matrix. All the equations in the model are solved analytically, so average medicine concentration in the film is known function of time. Thus, to solve stated inverse problem it is sufficient to find unknown scalar parameters of known functions using least-squares framework. Expressions arising in the solution are complicated so non-gradient methods are preferrable for optimization. Applying described procedure to experimental data leads to a good accuracy and the results may be explained from physicochemical point of view. In particular, the film swelling doesn’t influence release rate. In fact, the diffusion rate during first hours of experiment is large, and the main part of the medicine is released before swelling starts to play important role.
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