Effects of Ethyl Benzoate on Performance, Morphology, and Erosion of PLGA Implants Formed In Situ

An in Situ forming implant (ISFI) is a novel drug delivery system used for protein and peptide delivery, especially for cancer treatment. An ISFI based on 33% (w/w) poly(D,L-lactide-co-glycolide)(PLGA; 50:50)/3% (w/w) leuprolide acetate (LA)/64% (w/w) N-methyl-2-pyrrolidone (NMP) was prepared for this study. After injection of the final formulation, which is a viscous liquid to an aqueous medium, it deforms to become a semisolid or solid matrix. The performance of this matrix was investigated on the basis of peptide release from it. Erosion and morphology of ISFI were also Studied. The effects of adding 12.89% (w/w) ethyl benzoate (EB) as a rate-modifying agent on performance, erosion, and morphology of ISFI were assessed. The implant containing EB showed very low burst release (5.53% +/- 0.829%) and the morphology turns to closed pore-like structures. After adding EB, the morphology turns to closed pore-like structures. This type of morphology has very close relation to the performance of the implant as well. Finally, the effect of EB on performance, erosion, and morphology is explained by means of solvent-nonsolvent affinity, water permeation, and the rate of phase inversion. (C) 2008 Wiley Periodicals, Inc. Adv Polym Techn 27:17-26, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20114