The Selim and Rachel Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Israel.
Drug Dev Ind Pharm. 2012 Aug;38(8):940-51. doi: 10.3109/03639045.2011.634808. Epub 2012 Feb 10.
To introduce guidelines in selecting the particle size distribution (n(0), cm(-1)) that will guarantee optimal oral absorption for drugs with low solubility.
Unlike other multi-compartmental models the gastrointestinal tract is modeled as a continuous tube with spatially varying properties. The transport through the intestinal lumen is described using the dispersion model. The model accounts for the dissolution of poly-dispersed powders.
The model was used to examine the sensitivity of the absorption on permeability (P) and water solubility (C(s)) following administration in different log-normal powders. The absorption exhibits inverse sigmoidal dependence on the mean particle size (r(m), µm) regardless of the administrated dose or drug properties. Thus, there is an optimal r(m) that maximizes the benefit-cost ratio of the formulation; finer particles do not improve the absorption while coarser particles decrease it. Using the model we find that the optimal r(m) depends mainly on the drug C(s) and on the geometrical standard deviation (gSTD).
The results of this work provide the formulator with guidelines to select both r(m) and gSTD that guarantee optimal absorption.
介绍用于选择粒径分布（n(0)，cm(-1)）的指南，以保证低溶解度药物的最佳口服吸收。
与其他多隔室模型不同，胃肠道被建模为具有空间变化特性的连续管。使用弥散模型描述肠腔中的传输。该模型考虑了多分散粉末的溶解。
该模型用于研究在不同对数正态粉末中给药后，吸收对通透性（P）和水溶解度（C(s)）的敏感性。吸收表现出与平均粒径（r(m)，µm）的逆西格玛依赖性，而与给药剂量或药物性质无关。因此，存在一个最佳的 r(m)，它使配方的收益成本比最大化；更细的颗粒不会改善吸收，而更粗的颗粒则会降低吸收。使用该模型，我们发现最佳的 r(m)主要取决于药物 C(s)和几何标准偏差（gSTD）。
这项工作的结果为制剂师提供了指南，以选择保证最佳吸收的 r(m)和 gSTD。
