The mechanism behind the biphasic pulsatile drug release from physically mixed poly(DL-lactic(-co-glycolic) acid)-based compacts

Publication date: Available online 14 September 2018Source: International Journal of PharmaceuticsAuthor(s): Max Beugeling, Niels Grasmeijer, Philip A. Born, Merel van der Meulen, Renée S. van der Kooij, Kevin Schwengle, Lieven Baert, Katie Amssoms, Henderik W. Frijlink, Wouter L.J. HinrichsAbstractSuccessful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees’ comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(DL-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous fl...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research