Formation of Nanoparticles of a Hydrophilic Drug using Supercritical CO_2 and Microencapsulation for Sustained Release

摘要

The objective of this work was to develop sustained release formulation for hydrophilic drugs with minimal burst effects. For this purpose, nanoparticles of a hydrophilic drug were produced using supercritical CO_2, which were then encapsulated into polymer microparticles using an anhydrous method, followed by studying their sustained in-vitro drug release. A hydrophilic drug, dexamethasone phosphate, was dissolved in methanol and injected in supercritical CO_2 with ultrasonic field for enhanced molecular mixing (SAS-EM technique). Supercritical CO_2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles of 150 nm. These nanoparticles, on encapsulation in poly(lactide-co-glycolide) polymer using anhydrous s/o/o/o technique, resulted in the well-dispersed encapsulation of drug nanoparticles in polymer microspheres of ～70 μm. Their in-vitro drug release showed sustained release of-dexamethasone phosphate over a period of 700 hours with almost no initial burst release.