Department of Pharmacy and Pharmaceutical Technology, Facultad de Farmacia, Universidad de Sevilla, C/Profesor García González 2, 41012, Seville, Spain.
Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Hofackestrasse 30, 4132, Muttenz, Switzerland.
Pharm Res. 2019 Sep 6;36(11):156. doi: 10.1007/s11095-019-2685-5.
Pharmaceutical formulations are complex systems consisting of active pharmaceutical ingredient(s) and a number of excipients selected to provide the intended performance of the product. The understanding of materials' properties and technological processes is a requirement for building quality into pharmaceutical products. Such understanding is gained mostly from empirical correlations of material and process factors with quality attributes of the final product. However, it seems also important to gain knowledge based on mechanistic considerations. Promising is here to study morphological and/or topological characteristics of particles and their aggregates. These geometric aspects must be taken into account to better understand how product attributes emerge from raw materials, which includes, for example, mechanical tablet properties, disintegration or dissolution behavior. Regulatory agencies worldwide are promoting the use of physical models in pharmaceutics to design quality into a final product. This review deals with pharmaceutical applications of theoretical models, focusing on percolation theory, fractal, and multifractal geometry. The use of these so-called fractal approaches improves the understanding of different aspects in the development of solid dosage forms, for example by identifying critical drug and excipient concentrations, as well as to study effects of heterogeneity on dosage form performance. The aim is to link micro- and macrostructure to the emerging quality attributes of the pharmaceutical solid dosage forms as a strategy to enhance mechanistic understanding and to advance pharmaceutical development and manufacturing processes.
药物制剂是由活性药物成分（s）和许多辅料组成的复杂系统，这些辅料的选择是为了提供产品的预期性能。了解材料的性质和工艺过程是将质量构建到药物产品中的要求。这种理解主要是通过对材料和工艺因素与最终产品质量属性的经验相关性获得的。然而，基于机械考虑获得知识似乎也很重要。有前途的方法是研究颗粒及其聚集体的形态和/或拓扑特征。这些几何方面必须考虑在内，以更好地理解产品属性如何从原材料中出现，这包括例如机械片剂性质、崩解或溶解行为。全球监管机构都在推动在药剂学中使用物理模型来设计最终产品的质量。这篇综述讨论了理论模型在药物制剂中的应用，重点是渗流理论、分形和多重分形几何。这些所谓的分形方法的使用提高了对固体制剂开发中不同方面的理解，例如通过确定关键药物和赋形剂浓度，以及研究异质性对剂型性能的影响。目的是将微观结构和宏观结构与药物固体制剂的新兴质量属性联系起来，作为增强机械理解和推进药物开发和制造过程的策略。
