Budiman Arif, Lailasari Eli, Nurani Neng Vera, Yunita Ellen Nathania, Anastasya Gracia, Aulia Rizqa Nurul, Lestari Ira Novianty, Subra Laila, Aulifa Diah Lia
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia.
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia.
Pharmaceutics. 2023 Aug 10;15(8):2116. doi: 10.3390/pharmaceutics15082116.
The prevalence of active pharmaceutical ingredients (APIs) with low water solubility has experienced a significant increase in recent years. These APIs present challenges in formulation, particularly for oral dosage forms, despite their considerable therapeutic potential. Therefore, the improvement of solubility has become a major concern for pharmaceutical enterprises to increase the bioavailability of APIs. A promising formulation approach that can effectively improve the dissolution profile and the bioavailability of poorly water-soluble drugs is the utilization of amorphous systems. Numerous formulation methods have been developed to enhance poorly water-soluble drugs through amorphization systems, including co-amorphous formulations, amorphous solid dispersions (ASDs), and the use of mesoporous silica as a carrier. Furthermore, the successful enhancement of certain drugs with poor aqueous solubility through amorphization has led to their incorporation into various commercially available preparations, such as ASDs, where the crystalline structure of APIs is transformed into an amorphous state within a hydrophilic matrix. A novel approach, known as ternary solid dispersions (TSDs), has emerged to address the solubility and bioavailability challenges associated with amorphous drugs. Meanwhile, the introduction of a third component in the ASD and co-amorphous systems has demonstrated the potential to improve performance in terms of solubility, physical stability, and processability. This comprehensive review discusses the preparation and characterization of poorly water-soluble drugs in ternary solid dispersions and their mechanisms of drug release and physical stability.
近年来,低水溶性活性药物成分(API)的比例显著增加。尽管这些API具有相当大的治疗潜力,但它们在制剂方面存在挑战,尤其是对于口服剂型。因此,提高溶解度已成为制药企业提高API生物利用度的主要关注点。一种有前景的制剂方法是利用无定形体系,它可以有效改善难溶性药物的溶出曲线和生物利用度。已经开发了许多通过无定形化系统增强难溶性药物的制剂方法,包括共无定形制剂、无定形固体分散体(ASD)以及使用介孔二氧化硅作为载体。此外,通过无定形化成功提高了某些水溶性差的药物的性能,使其被纳入各种市售制剂中,如ASD,其中API的晶体结构在亲水性基质中转变为无定形状态。一种称为三元固体分散体(TSD)的新方法已经出现,以应对与无定形药物相关的溶解度和生物利用度挑战。同时,在ASD和共无定形系统中引入第三种成分已显示出在溶解度、物理稳定性和可加工性方面改善性能的潜力。这篇综述讨论了三元固体分散体中难溶性药物的制备、表征及其药物释放和物理稳定性机制。