Instant Formulation of Inhalable Beclomethasone Dipropionate-Gamma-Cyclodextrin Composite Particles Produced Using Supercritical Assisted Atomization.

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.

Immediate Release Formulation of Inhaled Beclomethasone Dipropionate-Hydroxypropyl-Beta-Cyclodextrin Composite Particles Produced Using Supercritical Assisted Atomization.

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.

Characterization and Aerosolization Performance of HydroxyPropyl-Beta-Cyclodextrin Particles Produced Using Supercritical Assisted Atomization.

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.

Formation of Polyethylene Glycol Particles Using a Low-Temperature Supercritical Assisted Atomization Process.

Polyethylene glycol (PEG) particles were prepared using low-temperature supercritical assisted atomization (LTSAA) with carbon dioxide as the spraying medium or the co-solute and acetone as the solvent. The effects of several key factors on the particle size were investigated. These factors included the concentration of the PEG solution, precipitator temperature, saturator temperature, ratio of the volumetric flow rate of carbon dioxide to the PEG solution, and the molecular weight of PEG. Spherical and non-aggregated PEG particles, with a mean size of 1.7-3.2 µm, were obtained in this study. The optimal conditions to produce fine particles were found to be a low concentration of the PEG solution, a low precipitator temperature, and low molecular weight of the PEG. The phase behavior of the solution mixture in the saturator presented a qualitative relationship. At the optimized volumetric flow rate ratios, the composition of CO2 in the feed streams was near the bubble points of the saturator temperatures. X-ray and differential scanning calorimetry analyses indicated that LTSAA-treated PEG had a reduced degree of crystallinity, which could be modulated via the precipitator temperature. PEG microparticles prepared by a LTSAA process would be promising carriers for drug-controlled formulations of PEG-drug composite particles.