RESUMO
Medical composites derived from Gamma-cyclodextrin (γ-CD) and beclomethasone dipropionate-gamma-cyclodextrin (BDP-γ-CD) are synthesized over supercritical-assisted atomization (SAA) herein. Carbon dioxide, which serves the dual function of spraying medium and co-solute, is incorporated in this process along with the ethanolic solvent. Results indicate that, for fine spherical particles, optimized aerosol performance could be obtained with 50.0% (w/w) ethanolic solvent, precipitator, and saturator at 373.2 K and 353.2 K, respectively, and carbon dioxide-to-γ-CD flow ratio of 1.8 in the presence of 10 wt% leucine (LEU) as dispersion enhancer. It is also noted that γ-CD solution at low concentration typically renders better aerosol performance of the particles. During drug particle-derivation, the solubility of drug BDP elevated considerably due to the formation of inclusion complexes, further assisted by the ethanolic solvent which increases the lipophilicity of BDP. Meanwhile, the in vitro aerosolization and dissolution performance of drug composites derived from varied γ-CD-to-BDP mass ratio (Z) were also evaluated. It was found that high Z promises higher fine particle fraction in the obtained drug composite while the dissolution rate of active ingredient (BDP) exhibits positive correlation to the content of water-soluble excipient (γ-CD) in the formulation. This study offers a new avenue for instant drug formulation with promising pulmonary delivery over the SAA technique.
RESUMO
In this study, the enhanced solubilization performance of a poorly soluble drug, beclomethasone dipropionate (BDP), was investigated using hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and ethanol. The enhanced solubility of the drug was determined using the phase solubility method and correlated as a function of both HP-ß-CD and ethanol concentrations. The effective progress of drug solubility originated from the formation of cyclodextrin and BDP inclusion complexes and increase in the lipophilicity of the medium, by aqueous ethanol, for hydrophobic BDP. BDP and HP-ß-CD composite particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium, 54.2% (w/w) aqueous ethanol as the solvent, and an optimal amount of the dispersion enhancer leucine. The effect of the mass ratio of HP-ß-CD to BDP (Z) on the in vitro aerosolization and in vitro dissolution performance of BDP-HP-ß-CD composite particles was evaluated. The aerosolization performance showed that the fine particles fraction (FPF) of the composite particles increased with increasing mass ratio. The water-soluble excipient (HP-ß-CD) effectively enhance the dissolution rate of BDP from composite particles. This study suggests that BDP-HP-ß-CD composite particles produced using SAA can be employed in immediate-release drug formulations for pulmonary delivery.
