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R. Shi, P. M. Hughes; Impact of Phase Behaviors of Polymer-drug Matrices on Drug Release Rate of Intravitreal Implants. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5994.
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To develop intravitreal implants for the treatment of ophthalmic conditions in posterior segment of eye and investigate factors influencing drug release kinetics.
Biodegradable polymeric implants loaded with a hydrophobic drug compound were developed using poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) as the matrices. The polymers and the drug were mixed at various ratios by solvent casting method. The mixtures were dried under vacuum and then fabricated into rod-like implants by melt extrusion. Two formulations were evaluated in this study which contained PLA and PLGA at different ratios. In vitro release rate was determined using HPLC. Morphology and phase behaviors of the implants were examined using Scanning Electron Microscopy (SEM) and Confocal Raman Microscopy (CRM).
Drug release from the implants containing higher percentage of PLA was much faster than that from the implants with lower PLA content. Within the first 5 days, 45% of the initially loaded drug was released from the implants with higher PLA content compared to 19% from the ones with lower PLA content. This result was counter-intuitive since the implants containing higher percentage of PLGA was expected to release faster due to its lower glass transition temperature. It was found that the unexpected release rates were caused by phase behaviors of the polymeric matrices. SEM and CRM data suggested that two phases were present in the implants: a drug-rich phase and a polymer-rich phase. The drug rich phase contained mainly PLGA and the drug compound while the polymer rich phase mainly PLA. Drug release was primarily from the drug rich phase and the drug to polymer ratio in the drug rich phase had a significant impact on the release rate.
The results of this study suggest that phase behaviors have significant impact on drug release kinetics and could be used in formulation design to achieve controlled drug release.
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