Chaves Luise L, Vieira Alexandre C C, Reis Salette, Sarmento Bruno, Ferreira Domingos C
Department of Applied Chemistry, Faculty of Pharmacy - University of Porto, Rua Jorge Viterbo Ferreira, 228, Edifício 3, piso 2, Postal Code: 4050-313 Porto, Portugal.
Curr Drug Deliv. 2014;11(2):253-69. doi: 10.2174/1567201811666140211110943.
The poor water solubility tops the list of undesirable physicochemical properties in the drug discovery and Solid Dispersions (SDs) has been frequently used to enhance dissolution of such compounds. Although, some challenges limit the studies of SD commercial application. During recent years, the Quality by Design (QbD) approach has begun to change drug development, and focus on pharmaceutical production, which shifted from an univariate empirical understanding for a systematic multivariate process. In this review, some possible variables during the development process, formulation and production of SDs were defined, introducing and applying the QbD concept. The proposed work presented important definitions as well as its application in the pharmaceutical product and process design, especially the challenges encountered during the development of formulations of poorly soluble drugs. In this aspect, the SD technique was deeply discussed, in which some important parameters during SD design and production were mentioned as method of production, polymers commonly used, methods for characterization and stability evaluation, in addition of biopharmaceutical considerations. Finally, a specific risk assessment for the design and production of SD and critical points were discussed, which was a positive evolution and may lead to better understanding of SD for a rational formulation.
在药物研发中，水溶性差是最不理想的物理化学性质之一，而固体分散体（SDs）已被频繁用于提高此类化合物的溶出度。然而，一些挑战限制了固体分散体商业应用的研究。近年来，质量源于设计（QbD）方法已开始改变药物研发，并聚焦于药物生产，这一过程从单变量的经验性理解转变为系统性的多变量过程。在本综述中，定义了固体分散体研发过程、制剂和生产过程中的一些可能变量，介绍并应用了QbD概念。所提出的工作给出了重要定义及其在药品和工艺设计中的应用，特别是在难溶性药物制剂研发过程中遇到的挑战。在这方面，对固体分散体技术进行了深入讨论，其中提到了固体分散体设计和生产过程中的一些重要参数，如生产方法、常用聚合物、表征方法和稳定性评估，以及生物药剂学方面的考虑。最后，讨论了固体分散体设计和生产的特定风险评估及关键点，这是一个积极的进展，可能有助于更合理地理解固体分散体以进行制剂设计。
