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Preparation of budesonide and budesonide-PLA microparticles using supercritical fluid precipitation technology

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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-μm 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°C. Using the PCA process, budesonide and budesonide-PLA microparticles with mean diameters of 1 to 2 μm were prepared. An increase in budesonide concentration (0.25%–1% wt/vol) resulted in budesonide microparticles that were fairly spherical and less aggiomerated. 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 ∼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°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.

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Authors and Affiliations

  1. Department of Chemical Engineering, Auburn University, 36849, AL

    Todd M. Martin, Ryan Shulz & Christopher B. Roberts

  2. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 68198-6025, Omaha, NE

    Nagesh Bandi & Uday B. Kompella

Authors
  1. Todd M. Martin
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  2. Nagesh Bandi
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  3. Ryan Shulz
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  4. Christopher B. Roberts
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  5. Uday B. Kompella
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Correspondence to Uday B. Kompella.

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Published: September 26, 2002

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Martin, T.M., Bandi, N., Shulz, R. et al. Preparation of budesonide and budesonide-PLA microparticles using supercritical fluid precipitation technology. AAPS PharmSciTech 3, 18 (2002). https://doi.org/10.1208/pt030318

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