Plasticizer concentration and the performance of a diffusion-controlled polymeric drug delivery system

A study of the competing effects of two plasticizers on the drug release from a diffusion-controlled, polymeric drug delivery system (PDDS) is presented. The formulation was prepared by hot melt extrusion and consisted of soluble starch as the polymer, theophylline as the drug and sorbitol as plasticizer. Through measurement of physical properties, it was demonstrated that both water and sorbitol antiplasticize soluble starch. At low water concentrations, the mechanical strength of the compacts made from soluble starch increased with increasing water concentration. With even higher water concentrations, the strength of the starch compacts began to decrease. A similar trend for mechanical properties was obtained for hot melt extrudates as a function of sorbitol concentration. The drug release profiles obtained exhibit two valleys, which can be explained as the simultaneous plasticizing effect of water from the dissolution medium and the antiplasticizing effect of sorbitol from the formulation. An important consequence is that significant unexplained variability in drug release from sustained release PDDS is possible as a result of small fluctuations in plasticizer concentration in the formulation if antiplasticizing effects are not considered as part of formulation development.