Physical characterization of multiparticulate systems

ABSTRACT The search for new pharmaceutical dosage forms and different drug delivery systems already used in therapeutics is a global trend, serving as an opportunity to expand the portfolio for the pharmaceutical industry. In this context, multiparticulate systems, such as pellets, granules, and minitablets, represent an attractive alternative, given the range of possibilities they provide. Among the methods used in the production of these systems, we highlight the process of extrusion-spheronization for pellet manufacture, wet granulation and hot-melt extrusion for the obtention of granules, and direct compression for minitablets. Although highly versatile, depending on the technology chosen, many processes and formulation variables can influence the ensuing stages of manufacture, as well as the final product. Therefore, the characterization of these small units is of fundamental importance for achieving batch homogeneity and optimal product performance. Analyses, including particle size distribution, morphology, density, porosity, mechanical strength and disintegration, are example tests used in this characterization. The objective of this review was to address the most widely used tests for the physical evaluation of multiparticulate systems.

摘要 研发新型药用剂型与已应用于临床治疗的各类药物递送系统是当前全球趋势，可为制药行业拓展产品管线提供契机。在此背景下，微丸（pellets）、颗粒（granules）与微片（minitablets）等多单元颗粒系统凭借其丰富的应用可能性，成为极具吸引力的研发选择。在这类系统的常用制备方法中，微丸制备常采用挤出-滚圆法（extrusion-spheronization），颗粒制备可选用湿法制粒（wet granulation）与热熔挤出法（hot-melt extrusion），微片制备则多采用直接压片法。尽管此类技术具备高度通用性，但根据所选工艺的不同，诸多工艺参数与处方变量均可能对后续制备环节及最终产品质量产生影响。因此，对这些小型单元进行表征，对保障批次均一性与产品最佳性能至关重要。该表征常用的检测项目包括粒径分布（particle size distribution）、形貌（morphology）、密度、孔隙率（porosity）、机械强度（mechanical strength）与崩解时限（disintegration）等。本综述旨在梳理多单元颗粒系统物理表征领域应用最广泛的检测方法。