Experimental study of the GAS process for producing microparticles of beclomethasone-17,21-dipropionate suitable for pulmonary delivery.
In this study the micronization of beclomethasone-17,21-dipropionate (BECD), used as an inhaled steroid for the treatment of asthma, was studied using the gas-antisolvent (GAS) process as a "green" alternative to pharmaceutical recrystallization. A systematic investigation of the influence of the key GAS process parameters: antisolvent addition rate (1, 50, 75 and 100 ml/min), temperature (25, 32.5, 40 and 52.5 degrees C), solute concentration (5, 25, 70 and 100%), and agitation rate (500, 1000, 2000 and 3000 rpm) were investigated on particle morphology, size distribution, and crystallinity. It was found using scanning electron microscopy (SEM) and laser diffraction, that increasing the antisolvent addition rate and the agitation rate, while decreasing the temperature and solute concentration, led to a decrease in the steroids mean particle diameter. These parameters could be tuned to give a mean particle diameter of 1.8 microm, and an average mass median aerodynamic diameter (MMAD) of 7.9 microm. High-performance liquid chromatography (HPLC) results showed the recrystallized BECD was purer than the non-processed material. The role of the solvent (acetone, methanol and ethanol) in the BECD crystal structure was investigated using X-ray diffraction (XRD), which showed acetone gave a more crystalline structure, hence having lower incorporation into the crystal structure. These results showed that the GAS process has the potential to produce steroid with powder properties suitable for inhalation therapy.
Bakhbakhi
Yousef
Y
Department of Chemical and Biochemical Engineering, University of Western Ontario, London, Ont., Canada N6A 5B9.
Charpentier
Paul A
PA
Rohani
Sohrab
S
D000096:Acetone / Q000737:chemistry; D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D003460:Crystallization; D010316:Particle Size; D011208:Powders; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D000893:Anti-Inflammatory Agents; D011208:Powders; D012997:Solvents; D000096:Acetone; D002245:Carbon Dioxide; D001507:Beclomethasone