Formation of Nanoparticles of a Hydrophilic Drug using Supercritical CO2 and Microencapsulation for Sustained Release

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 CO2, 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 CO2 with ultrasonic field for enhanced molecular mixing (SAS-EM technique). Supercritical CO2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles of 150 nm. These nanoparticles, on encapsulation in poly(lactideco-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 invitro drug release showed sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release.