Engineering drug ultrafine particles of beclomethasone dipropionate for dry powder inhalation.
Beclomethasone dipropionate (BDP), which is a member in the inhaled glucocorticosteroid class, is commonly used in the treatment of asthma by pulmonary delivery. The purpose of this study is to prepare ultrafine BDP particles for dry powder inhalation (DPI) administration by combining microfluidic antisolvent precipitation without surfactant, high-pressure homogenization (HPH) and spray drying. T-junction microchannel was adopted for the preparation of needle-like BDP particles. The needle-like particles could be easily broken down into smaller particles during HPH, which were assembled into uniform low-density spherical BDP aggregates by spray drying. The effects of the operation parameters, such as the flow rates of BDP methanol solution and antisolvent, the overall flow rate, the BDP concentration, and the change of the injection phase on BDP particle size were explored. The results indicated that the BDP particle size greatly decreased with the reduction of BDP solution flow rate and the increase of antisolvent flow rate. However, the BDP particle size firstly decreased and then increased with the increase of the overall flow rate and the increase of BDP concentration. Also, BDP solution as the injection phase could form the smaller BDP particles. 10 HPH cycles are enough to forming short rod-like particles. After spray drying, the BDP spherical aggregates with a 2-3 μm size could be achieved. They have an excellent aerosol performance, 2.8 and 1.4 times as many as raw BDP and vacuum-dried BDP particles, respectively.
State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
Li-Min
LM
Xu
Qian-Xia
QX
Zhang
Yue
Y
Zhou
Hong
H
Zhao
Jie-Xin
JX
Wang
Jian-Feng
JF
Chen
D000280:Administration, Inhalation; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D018927:Anti-Asthmatic Agents; D001507:Beclomethasone