Role of Permeability on the Biopredictive Dissolution of Amorphous Solid Dispersions

Abstract

An ideal dissolution test for amorphous solid dispersions (ASDs) should reflect physicochemical, physiological, and hydrodynamic conditions which accurately represent in vivo dissolution. However, this is confounded by the evolution of different molecular and colloidal species during dissolution, generating a supersaturated state of the drug. The supersaturated state of a drug is thermodynamically unstable which drives the process of precipitation resulting in a loss of solubility advantage. Maintaining a supersaturated state of the drug with the help of precipitation inhibiting excipients is a key component in the design of ASDs. Therefore, a biopredictive dissolution test is critical for proper risk assessment during the development of an optimal ASD formulation. One of the overlooked components of biopredictive dissolution is the role of drug permeability. The kinetic changes in the phase behavior of a drug during dissolution of ASDs are influenced by drug permeability across a membrane. Conventionally, drug dissolution and permeation are analyzed separately although they occur simultaneously in vivo. The kinetic phase changes occurring during dissolution of ASDs can influence the thermodynamic activity and membrane flux of a drug. The present review evaluates the feasibility, predictability, and practicability of permeability/dissolution for the optimal development and risk assessment of ASD formulations. Graphical abstract