CONICET | Buscador de Institutos y Recursos Humanos

Biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) is widely used for drug delivery systems. Injectable fluid systems, with in-situ formation of the drug-loaded matrix, are practical dosage forms that represent an attractive alternative to replace conventional drug-eluting implants. These novel systems are prepared by dissolving both the hydrophobic polymer and drug in an organic solvent. When the solution comes in contact with water or physiological fluids, the solvent is diluted/eluted and the polymer precipitates entrapping the drug. In order to develop a progesterone-eluting platform based upon this concept, we perform an in-vitro experimental study to choose the polymer-solvent system that yields a higher hormone loading. Formulations of 20% and 40% w/w PLGA 50:50 (Resomer) comprising N-Methylpyrrolidone (NMP), Glycerol Formal (GF), 2-Pyrrolidone (2P) or Dimethyl Sulfoxide (DMSO) as solvents, with 5% and 10% w/w of progesterone (PRG), were tested. The fluid formulations were cast into an aqueous buffered solution (pH=7.4) to form the implant. After analysing the load and encapsulation efficiency of PRG, the following conclusions arisen up to the present in the range of studied experimental conditions: (a) At constant PLGA concentration, the higher the PRG loading, the higher the PRG entrapped. (b) At constant PRG concentration, the higher the PLGA concentration, the lower the entrapping. (c) At constant PRG-PLGA ratio, the entrapping efficiency is dependent on the PRG solubility in the organic solvent. Below saturation concentration, the lower the PRG solubility, the higher the entrapping efficiency. Above saturation concentration, the behaviour is opposite. Results from the present study show that PRG entrapping efficiencies higher than 60 % are workable. PRG-PLGA injectable fluid systems offer a promissory alternative approach to development in-situ forming PRG-eluting implants.