CHARACTERIZATION OF MICROSPHERES FORMED IN SITU FOR DRUG-CONTROLLED RELEASE

TURINO, L.N.; MARIANO, R.N.; CABRERA, M.I.; GRAU, R.J.A.

Rosario

Taller; 1º Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos; 2009

Centro Binacional (Argentina–Italia) de Criobiología Clínica y Aplicada (CAIC), la Facultad de Cs. Bioquímicas y Farmacéuticas (UNR) y la Soc. Latinoamericana de Biomateriales, Ingeniería de Tejidos y Órganos Artificiales (SLABO).

Resumen aprobado para su presentación los días 25, 26 y 27 de agosto de 2009. Biocompatible and biodegradable poly(lactic-co-glycolic) acid (PLGA) are widely used for drug delivery systems. Microspheres formed in situ are a novel and practical dosage form of the PLGA-based controlled release devices. They are prepared by dissolving the polymer and the drug in a solvent-system (phase 1) and then emulsified within a second solvent-system (phase 2). In order to develop a drug-eluting platform based upon this concept, we perform an experimental study to choose the most appropriate solvent-system that yields in situ formed microspheres. PLGA formulations comprising 2-Pyrrolidone (2P), Glycerol Formal (GF) and mixtures of GF and Triacetin (GFT) were tested as solvents forming the phase 1, while Miglyol 812 (M) was used as the oily phase 2. PLGA 50:50 (Resomer) solutions at 20 and 40% w/w in phase 1 were cast into phase 2 and vigorous stirred to form pre-microspheres. The resulting emulsion was cast into an aqueous buffered solution (pH=7.4) to form the microspheres. The microscopic characterization showed that the in situ formed microparticles are spherical and non-aggregated particles characterized by a Gaussian size distribution. The more hydrophobic phase 1 systems (GFT) yielded the highest mean size. The systems with 2P rendered a lower size but a great dispersion. For all solvent systems, the shape of the microspheres of 40% PLGA was more spherical than 20% PLGA, but GF conserved this shape at 20% more than others. The sphere surface was more porous for systems using GF than 2P. The GFT were not characterized. The best solvent was GF because the microspheres exhibited appropriate sizes and a more uniform distribution, at both high and low PLGA concentrations. Its higher surface porosity may increase the diffusion phenomena and erosion of PLGA. These characteristics make it a promising system for the controlled release of drugs.