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.
RESUMO
In this study, hydroxypropyl-beta-cyclodextrin (HP-ß-CD) particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium or co-solute and aqueous ethanol solution as the solvent. The effects of several key factors on the morphology and size of the HP-ß-CD particles were investigated. These factors included the solvent effect, temperatures of the precipitator and saturator, concentration of the HP-ß-CD solution, and flow rate ratio of carbon dioxide to the HP-ß-CD solution. The conducive conditions for producing fine spherical particles were 54.2% (w/w) aqueous ethanol as the solvent; precipitator and saturator temperatures of 373.2 K and 353.2 K, respectively; a flow rate ratio of carbon dioxide to HP-ß-CD solution of 1.8; and low concentrations of HP-ß-CD solution. The addition of leucine (LEU) enhanced the aerosol performance of the HP-ß-CD particles, and the fine particle fraction (FPF) of the HP-ß-CD particles with the addition of 13.0 mass% LEU was 1.8 times higher than that of the HP-ß-CD particles without LEU. This study shows that LEU can act as a dispersion enhancer and that HP-ß-CD particles produced using SAA can be used as pulmonary drug carriers.