丙酸倍氯米松醋酸乙酯溶剂化物的理化性质及其在制备混悬气雾剂中的应用

PHYSICOCHEMICAL CHARACTERISTICS OFBECLOMETHASONE DIPROPIONATE ETHYL ACETATESOLVATE AND ITS APPLICATION IN MDIs

制备了丙酸倍氯米松醋酸乙酯溶剂化物（１）及其微粉，用以制备丙酸倍氯米松混悬型气雾剂。分别对１及微粉的理化性质和制备的气雾剂的行为进行了考察。Ｘ衍射、热重分析及红外光谱测定结果证实醋酸乙酯以结合形式存在于１中。ＥｔＯＡｃ／１结合百分比约为９％。采用微粉化工艺制得３批样品的粒径分别为１．６８±０．６２、２．３４±１．６３、２．４４±０．５６μｍ。且微粉化过程无结合溶剂损失及晶型转化发生。外冲程实验表明，该气雾剂在肺深部的沉积达４５％以上。

Beclomethasone dipropionate ethyl acetate solvate (1), and its micronized powder were prepared. X-ray diffraction, DTA and IR spectrum showed that ethyl acetate existed in combined form up to about 9% in solvate crystal lattice in both crystalline solvate and micronized powder. Micronized powder had particle sizes of 1.68±0.62, 2.34±1.63 and 2.44±0.56 μm. No loss of combined solvent or crystal form transformation were observed during micronization. In vitro performance test implied that MDIs with potency of 50 μg/dose prepared with above micronized solvates had drug deposition in deep lung over 45%.