Effect of the nature of the polymer and of the process of drug release (diffusion or erosion) for oral dosage forms

Abstract

Conventional oral dosage forms with immediate release are associated with plasma drug levels alternating between high peaks and low troughs leading to harmful side effects. These side effects are reduced and the therapy is optimized by using oral dosage forms with controlled release. Usually these dosage forms consist of devices where the drug is dispersed through a biocompatible polymer, which plays the role of a matrix, and the polymer plays the major role for controlling the drug release along the gastrointestinal tract. Depending on the nature of the polymer, the process of drug release is different and the two extreme cases are considered: the one with stable polymers where the drug release is controlled by diffusion with the more simple case of constant diffusivity; the other with erodible polymers with a constant rate of erosion. As the gastrointestinal transit time is finite, the radius of spherical dosage forms is evaluated such that the time of drug delivery is 24 h. Various shapes are also considered with the same polymer and the same diffusivity or rate of erosion, by keeping the same volume and mass of drug for these dosage forms. Following these studies, the plasma drug level is also assessed for these two types of dosage forms. Some results of interest are obtained: for each type of polymer, the shape given to the dosage form exhibits some interest for the kinetics of drug release; the type of polymer is of prime importance, and erodible polymers are associated with a more constant plasma drug level. Thus these results take stock of the question of drug release by considering the properties of the polymer, whether it is stable with its diffusivity or it is erodible with its rate of erosion. Finally this knowledge makes possible the evaluation of the dimensions of dosage forms necessary for a given time of drug delivery and a given therapy.