Experimental study of the GAS process for producing microparticles of beclomethasone-17,21-dipropionate suitable for pulmonary delivery
Experimental study of the GAS process for producing microparticles of beclomethasone-17,21-dipropionate suitable for pulmonary delivery
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DOI：
10.1016/j.ijpharm.2005.11.008
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发表时间：
2006-02-17
影响因子：
5.8
通讯作者：
Rohani, S
中科院分区：
文献类型：
--
作者：
Bakhbakhi, Y;Charpentier, PA;Rohani, S
本研究采用气体-抗溶剂（GAS）工艺，研究了用于治疗哮喘的吸入类固醇倍氯米松-17,21-二丙酸（BECD）的微粉化，作为药物重结晶的“绿色”替代方法。系统考察了GAS关键工艺参数：抗溶剂添加量（1、50、75和100 ml/min）、温度（25、32.5、40和52.5℃）、溶质浓度（5、25、70和100%）和搅拌速度（500、1000、2000和3000 rpm）对颗粒形貌、粒度分布和结晶度的影响。通过扫描电镜（SEM）和激光衍射分析发现，增加抗溶剂加入速率和搅拌速率，同时降低温度和溶质浓度，会导致甾体平均粒径减小。这些参数可以调整为平均颗粒直径为1.8 μ m，平均质量中位数气动直径（MMAD）为7.9 μ m。高效液相色谱（HPLC）结果表明，再结晶BECD的纯度高于未加工的材料。用x射线衍射（XRD）研究了溶剂（丙酮、甲醇和乙醇）在BECD晶体结构中的作用，结果表明丙酮具有更强的晶体结构，因此在晶体结构中的掺入量更低。这些结果表明，气体过程有可能产生具有粉末性质的类固醇，适合吸入治疗。(c) 2005 Elsevier B.V.版权所有
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 mu m, and an average mass median aerodynamic diameter (MMAD) of 7.9 mu m. 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. (c) 2005 Elsevier B.V. All rights reserved.