Development of an in situ forming biodegradable poly-lactide-coglycolide system for the controlled release of proteins

Copolymers of polylactic acid (PLA) and polyglycolic acid (PGA) spontaneously form solid depots when a solution of the copolymer in a pharmaceutically acceptable solvent is injected into water. Key formulation variables which affect the performance of these systems were evaluated in the present study. The solubilities of various co-polymer ratios of PLGA were investigated as a function of the solvent solubility parameter, and it was found that the ideal range was 9–11 (cal/cm 3 ) 1/2 . The in vitro release into phosphate buffered saline of fluorescein-labeled bovine serum albumin was evaluated from systems dissolved in either dimethyl sulfoxide (DMSO) or N-methyl-2-pyrrolidone (NMP). For high molecular weight PLGA in NMP, the initial burst (which was found to be inversely proportional to polymer percent) is followed by zero-order release for up to 2 weeks. A significantly different release pattern is observed with DMSO. With low molecular weight PLGA in DMSO or NMP, it was possible to totally eliminate the initial burst, and have zero-order delivery for at least 1 week.