Elevated temperature accelerated release testing of PLGA microspheres.
Drug release from four different poly(lactic-co-glycolic) acid (PLGA) microsphere formulations was evaluated under "real-time" (37 degrees C) and accelerated release testing conditions of elevated temperature (45, 53, 60 and 70 degrees 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 degrees 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.
Zolnik
Banu S
BS
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
Leary
Pauline E
PE
Burgess
Diane J
DJ
D002626:Chemistry, Pharmaceutical; D006358:Hot Temperature; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*; D013696:Temperature
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid