Critical points in the formulation of pharmaceutical swellable controlled release dosage forms——Influence of particle size

摘要

Swellable matrix represents one of the most employed controlled release systems. These dosage forms provide slow release of drugs to reduce the fluctuation of drug concentration in plasma in order to improve the efficiency of treatment and/or to reduce adverse effects. The application of the concepts of statistical physics has allowed discovering the existence of critical points in the formulation of swellable matrices. These points, representing the volume fractions of the tablet components where the properties of the matrix diverge or change suddenly, provide important knowledge of how to rationalize the design of swellable matrices. The critical points are generally related to the percolation threshold of one of the components of the formulation, which corresponds to a geometrical phase transition of this component, passing from isolation to spanning the whole system. The last section of the paper is devoted to more recent findings concerning the influence of particle size of the components on the percolation threshold of the matrix forming polymer, and therefore on the release behaviour of the matrix. Knowledge of the excipient percolation threshold allows a more rational design of swellable matrices, according to the guidelines of the regulatory authorities concerning science-based formulation and quality by design.