Elevated temperature accelerated release testing of PLGA microspheres

    loading  Checking for direct PDF access through Ovid

Abstract

Drug release from four different poly(lactic-co-glycolic) acid (PLGA) microsphere formulations was evaluated under “real-time” (37 °C) and accelerated release testing conditions of elevated temperature (45, 53, 60 and 70 °C) and increase in flow rate (4–35 ml/min) using United States Pharmacopeia (USP) apparatus 4. Formulation 5 K (composed of low Mw PLGA) exhibited diffusion-controlled kinetics in “real-time”. Whereas, formulations 25 K, 28 K and 70 K (composed of medium and high Mw PLGA) followed erosion-controlled kinetics at 37 °C. Temperature-induced degradation of the microspheres was studied by monitoring drug release rates, change in molecular weight and morphological changes. Drug release rates at elevated temperature were used to predict “real-time” release applying the Arrhenius equation. The energy of activation for dexamethasone release from PLGA microspheres was calculated as 19.14 kcal/mol. Molecular weight change measured by gel permeation chromatography followed first order kinetics for both “real-time” and accelerated release. All four formulations exhibited morphological changes (such as surface pore closing and geometry change) at elevated temperature with consequent reduction in burst release.

Related Topics

    loading  Loading Related Articles