Instantaneous coprecipitation of polymer/drug microparticles using the supercritical assisted injection in a liquid antisolvent

Abstract

In this work, the supercritical assisted injection in a liquid antisolvent (SAILA) has been proposed as a new technique to produce composite microparticles for drug controlled release. Coprecipitation has been attempted for different non-steroidal anti-inflammatory drugs (Diclofenac, DF, Piroxicam, PX, and Indomethacin, ID) using poly-lactic-co-glycolic (PLGA) as the polymer matrix; acetone has been used as the liquid solvent and water as the liquid antisolvent. Coprecipitation was successful in all the cases and encapsulation efficiency ranged between 50 and 97%. The effect of operating parameters, such as the polymer/drug ratio, polymer concentration, injection temperature and pressure on particle morphology and drug release rate has been studied considering the system PLGA/Piroxicam. SEM analysis indicated that non-coalescing spherical microparticles formed by PLGA/PX were produced by SAILA at fast mixing conditions (higher injection pressure and higher temperature) and high polymer/drug ratios (20/1 and 10/1). All coprecipitates showed a sharp particle distribution, with diameters ranging between about 0.28 and 2.50μm.SAILA composite microparticles have been characterized by X-ray, FT-IR, EDX and UV–vis analysis. PLGA/PX coprecipitates showed a prolonged release, about 7 times slower than the physical mixture of the same compounds; moreover, the polymer/drug ratio and the concentration of polymer in the solvent revealed to be a controlling parameter for drug release. The Hoffenberg’s equation has been used to describe experimental data, showing a fair good agreement with PX release data.