Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release

Abstract 

Purpose

Our purpose was to produce nanoparticles of a hydrophilic drug with use of supercritical carbon dioxide (CO₂), encapsulate the obtained nanoparticles into polymer microparticles with use of an anhydrous method and study their sustained in vitro drug release.

Methods

The hydrophilic drug, dexamethasone phosphate, is dissolved in methanol and injected in supercritical CO₂ with an ultrasonic field for enhanced molecular mixing (supercritical antisolvent technique with enhanced mass transfer [SAS-EM]). Supercritical CO₂ rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles. The nanoparticles are then encapsulated in poly(lactide-co-glycolide) (PLGA) polymer by use of the anhydrous solid-oil-oil-oil technique. This results in a well-dispersed encapsulation of drug nanoparticles in polymer microspheres. In vitro drug release from these microparticles is studied.

Results

With supercritical CO₂ used as an antisolvent, nanoparticles of dexamethasone phosphate were obtained in the range of 150 to 200 nm. On encapsulation in polylactide coglycolide, composite microspheres of ∼70 μm were obtained. The in vitro drug release of these nanoparticles/microparticles composites shows sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release.

Conclusions

Nanoparticles of dexamethasone phosphate can be produced with the SAS-EM technique. When microencapsulated, these particles can provide sustained drug release without initial burst release. Because the complete process is anhydrous, it can be easily extended to produce sustained release formulations of other hydrophilic drugs.

Key words: Sustained/controlled drug release, Dexamethasone phosphate, Polylactide coglycolide, Supercritical antisolvent technique with enhanced mass transfer, Solid-oil-oil-oil, Supercritical, Nanoparticle, SASEM