title: Preparation of budesonide and budesonide-PLA microparticles using supercritical fluid precipitation technology.
abstract: The objective of this study was to prepare and characterize microparticles of budesonide alone and budesonide and polylactic acid (PLA) using supercritical fluid (SCF) technology. A precipitation with a compressed antisolvent (PCA) technique employing supercritical CO2 and a nozzle with 100- microm internal diameter was used to prepare microparticles of budesonide and budesonide-PLA. The effect of various operating variables (temperature and pressure of CO2 and flow rates of drug-polymer solution and/or CO2) and formulation variables (0.25%, 0.5%, and 1% budesonide in methylene chloride) on the morphology and size distribution of the microparticles was determined using scanning electron microscopy. In addition, budesonide-PLA particles were characterized for their surface charge and drug-polymer interactions using a zeta meter and differential scanning calorimetry (DSC), respectively. Furthermore, in vitro budesonide release from budesonide-PLA microparticles was determined at 37 degrees C. Using the PCA process, budesonide and budesonide-PLA microparticles with mean diameters of 1 to 2 microm were prepared. An increase in budesonide concentration (0.25%-1% wt/vol) resulted in budesonide microparticles that were fairly spherical and less agglomerated. In addition, the size of the microparticles increased with an increase in the drug-polymer solution flow rate (1.4-4.7 mL/min) or with a decrease in the CO2 flow rate (50-10 mL/min). Budesonide-PLA microparticles had a drug loading of 7.94%, equivalent to approximately 80% encapsulation efficiency. Budesonide-PLA microparticles had a zeta potential of -37 +/- 4 mV, and DSC studies indicated that SCF processing of budesonide-PLA microparticles resulted in the loss of budesonide crystallinity. Finally, in vitro drug release studies at 37 degrees C indicated 50% budesonide release from the budesonide-PLA microparticles at the end of 28 days. Thus, the PCA process was successful in producing budesonide and budesonide-PLA microparticles. In addition, budesonide-PLA microparticles sustained budesonide release for 4 weeks.
authors.affiliation: Department of Chemical Engineering, Auburn University, AL 36849, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Martin
authors.forename: Nagesh
authors.initials: N
authors.lastname: Bandi
authors.forename: Ryan
authors.initials: R
authors.lastname: Shulz
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Roberts
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
mesh_terms: D019819:Budesonide / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002245:Carbon Dioxide / Q000737:chemistry; D011232:Chemical Precipitation; D003692:Delayed-Action Preparations / Q000378:metabolism; D003956:Dialysis; D004058:Diffusion; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D017022:Flow Injection Analysis; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013696:Temperature
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D012996:Solutions; D002245:Carbon Dioxide; D019344:Lactic Acid; C033616:poly(lactide); D019819:Budesonide