Substance Properties

Abstract

With the goal of achieving an IVIVC, the required intrinsic physicochemical information will include the pH-solubility profile, stability in the gastrointestinal environment, and other dissolution-controlling variables of the drug substance that are related to the extremes of the physiological environment experienced by the dosage form. Permeability, another drug substance property, can be determined in vitro by cellular permeability models such as Caco-2 cells. Drug Product Properties The purpose of in vitro performance testing is to challenge the dosage forms under different conditions to predict the in vivo performance. The primary characterization is related to the rate-determining mechanism with different considerations for each release pattern. Immediate-release dissolution is a stochastic process but extended-release and delayed-release have intentional modifications that enable the performance characteristics. The variables of importance for immediate-release would include but not be limited to wetting, disintegration, disaggregation, erosion, and dissolution of particles in suspension. In addition to factors critical to the in vivo performance of immediate-release formulations, the key variables of importance for delayed-release are onset of the dissolution and pH dependency. The rate-controlling mechanisms of importance for extended-release include but are not limited to erosion, diffusion, swelling, and osmotic pressure. Identification of the rate-limiting steps in the dissolution process that can be linked to in vivo performance is of great importance.