Abstract
Physico-chemical properties of an injectable polymeric implant system were evaluated and utilized to predict and understand the in vivo release of a model drug. The injectable implant system is based on the principle that a water insoluble polymer, dissolved in a biocompatible solvent, will precipitate upon contact with water. The solubility parameter of poly( dl-lactide) and dl-lactide-co-glycolide copolymers were experimentally determined by evaluating the solubility of these polymers in hydrogen bonding solvents having solubility parameters ranging from 8.9 to 14.8 (cal/cm 3) 1 2 . The appropriate Flory-Huggins interaction parameters were then calculated at 25 and 37°C. Analysis of ternary phase diagrams indicated that the quantity of water needed to initiate precipitation, as well as the precipitation threshold, increased with increasing temperature in agreement with theoretical calculations. Rats were subcutaneously administered formulations comprised of polymer concentrations above and below the precipitation threshold, i.e., 40% w/w polymer. Formulations with polymer concentrations below the precipitation threshold exhibited approximately twice the initial release compared to formulations having a polymer content above the precipitation threshold. A key factor affecting the initial release of a model drug from formulations was the polymer content of the formulation with respect to the precipitation threshold. The reported method of analysis may be utilized to screen polymers and biocompatible solvents for use in these injectable implant systems.
Published Version
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