Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release.
OBJECTIVE
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 approximately 70 microm 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.
Thote
Amol J
AJ
Department of Chemical Engineering, Auburn University, Auburn, Alabama 36849-5127, USA.
Gupta
Ram B
RB
D002214:Capsules / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D003460:Crystallization / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties
D002214:Capsules; D003692:Delayed-Action Preparations; D046911:Macromolecular Substances; D011108:Polymers; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C004180:dexamethasone 21-phosphate; D019344:Lactic Acid; D003907:Dexamethasone