Preparation of budesonide and budesonide-PLA microparticles using supercritical fluid precipitation technology.
- 1 January 2002
- journal article
- Vol. 3 (3) , E18
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.Keywords
This publication has 17 references indexed in Scilit:
- Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)European Journal of Pharmacology, 2002
- Fabrication, characterization and in vitro release of paclitaxel (Taxol®) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiersJournal of Controlled Release, 2001
- Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cellsEuropean Journal of Pharmacology, 2001
- Preparation of Drug Delivery Systems Using Supercritical Fluid TechnologyCritical Reviews in Therapeutic Drug Carrier Systems, 2001
- Preparation of Biodegradable Microparticles Using Solution-Enhanced Dispersion by Supercritical Fluids (SEDS)Pharmaceutical Research, 1999
- Application of Supercritical Carbon Dioxide for the Preparation of a Piroxicam-β-Cyclodextrin Inclusion CompoundPharmaceutical Research, 1999
- Production of drug loaded microparticles by the use of supercritical gases with the Aerosol Solvent Extraction System (ASES) processJournal of Microencapsulation, 1996
- High-performance liquid chromatographic method for the determination of budesonide in bronchoalveolar lavage of asthmatic patientsJournal of Chromatography B: Biomedical Sciences and Applications, 1995
- The hamster cheek pouch as a model in microcirculation research.1990
- Leukotriene B4-induced permeability increase in postcapillary venules and its inhibition by three different antiinflammatory drugsInflammation, 1989