Abstract:
Amorphous solid dispersion (ASD) technology is an attractive formulation approach for poorly soluble drugs because of the supersaturated state acquired during its dissolution. The high thermodynamic activity of the supersaturated state of the drug is also a driver for the enhanced absorptive flux across a membrane. However, this advantage can easily be lost due to the inherent instability of supersaturation, causing drug precipitation. Stabilizing the supersaturated state during the dissolution of ASD for the relevant absorption time frame is a challenging area in formulation research. Stabilizing the supersaturated state by using polymeric excipients and understanding the phase behavior of drugs during dissolution are required for the optimal performance of ASD formulations. A number of confounding kinetic, formulation and physiological factors can influence the evolution of supersaturation and phase changes during dissolution of ASDs. The review highlights the complex nature of dissolution of ASDs and the need of biorelevant dissolution for proper risk assessment and optimizing formulation development.
摘要:
无定形固体分散体(ASD)技术是溶解性差的药物的有吸引力的配制方法,因为在其溶解过程中获得过饱和状态。药物过饱和状态的高热力学活性也是跨膜吸收通量增强的驱动因素。然而,由于过饱和的固有不稳定性,这种优势很容易丧失,导致药物沉淀。在相关吸收时间范围内稳定ASD溶解期间的过饱和状态是制剂研究中的挑战性领域。ASD制剂的最佳性能需要通过使用聚合物赋形剂来稳定过饱和状态并了解药物在溶解过程中的相行为。一些混杂的动力学,配方和生理因素会影响ASD溶解过程中过饱和和相变的演变。该综述强调了ASD溶解的复杂性,以及生物相关溶解对适当风险评估和优化配方开发的需求。