Sridhar Duvvuri1, Kumar Gaurav Janoria, Ashim K Mitra. 1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005, Rockhill Road, Kansas City, Missouri 64110, USA.
Abstract
PURPOSE: The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS: Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer RG 502H [D,L-lactide:glycolide(50:50), MW 8000 Da], were employed in the preparation of PLGA microspheres. Five sets of microsphere batches were prepared with two pure polymers and their 1:3, 1:1, and 3:1 blends. Drug entrapment, surface morphology, particle size analysis, drug release, and differential scanning calorimetric studies were performed. In vitro drug-release data were fitted to a set of empirical sigmoidal equations by nonlinear regression analysis that could effectively predict various parameters that characterize both diffusion and degradation cum diffusion-controlled release phases of GCV. RESULTS: Entrapment efficiencies of GCV ranged from 47 to 73%. Higher amounts of GCV were entrapped in polymer blend microspheres relative to individual polymers. Triphasic GCV release profiles were observed, which consisted of both diffusion and degradation cum diffusion-controlled phases. In vitro GCV release was shortest for Resomer RG 502H microsphere (10 days) and longest for PLGA 7525 microspheres (90 days). Upon blending, the duration of release gradually decreased as the content of Resomer RG 502H in the matrix was raised. Equations effectively estimated the drug-release rate constants during both the phases with high R2 values (>0.990). GCV release was slower from the blend microsphere during the initial diffusion phase. Majority of entrapped drug (70-95%) was released during the matrix degradation cum diffusion phase. CONCLUSIONS: Drug entrapment and release parameters estimated by the equations indicate more efficient matrix packing between PLGA 7525 and Resomer RG 502H in polymer-blended microspheres. The overall duration of drug release diminishes with rising content of Resomer RG 502H in the matrix. Differential scanning calorimetry studies indicate stronger binding between the polymers in the PLGA 7525/Resomer RG 502HColon, two colons 3:1 blend. Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives.
PURPOSE: The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS: Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer RG 502H [D,L-lactide:glycolide(50:50), MW 8000 Da], were employed in the preparation of PLGA microspheres. Five sets of microsphere batches were prepared with two pure polymers and their 1:3, 1:1, and 3:1 blends. Drug entrapment, surface morphology, particle size analysis, drug release, and differential scanning calorimetric studies were performed. In vitro drug-release data were fitted to a set of empirical sigmoidal equations by nonlinear regression analysis that could effectively predict various parameters that characterize both diffusion and degradation cum diffusion-controlled release phases of GCV. RESULTS: Entrapment efficiencies of GCV ranged from 47 to 73%. Higher amounts of GCV were entrapped in polymer blend microspheres relative to individual polymers. Triphasic GCV release profiles were observed, which consisted of both diffusion and degradation cum diffusion-controlled phases. In vitro GCV release was shortest for Resomer RG 502H microsphere (10 days) and longest for PLGA 7525 microspheres (90 days). Upon blending, the duration of release gradually decreased as the content of Resomer RG 502H in the matrix was raised. Equations effectively estimated the drug-release rate constants during both the phases with high R2 values (>0.990). GCV release was slower from the blend microsphere during the initial diffusion phase. Majority of entrapped drug (70-95%) was released during the matrix degradation cum diffusion phase. CONCLUSIONS:Drug entrapment and release parameters estimated by the equations indicate more efficient matrix packing between PLGA 7525 and Resomer RG 502H in polymer-blended microspheres. The overall duration of drug release diminishes with rising content of Resomer RG 502H in the matrix. Differential scanning calorimetry studies indicate stronger binding between the polymers in the PLGA 7525/Resomer RG 502HColon, two colons 3:1 blend. Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives.
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