鲑鱼降钙素肺部干粉吸入剂的制备及含量影响因素的考察

目的喷雾干燥法制备鲑鱼降钙素(salmon calcitonin,sCT)肺部干粉吸入剂;考察溶液pH值、喷干温度和处方中泊洛沙姆(F68)的用量对鲑鱼降钙素含量的影响。方法分别制备不同pH值和不同F68用量的鲑鱼降钙素溶液,在不同温度下喷雾干燥制备鲑鱼降钙素干粉吸入剂粉末,用高效液相色谱仪对所制备的粉末进行含量测定。采用TSI装置测定粉末沉积率,用LS320激光粒度测定仪测定粒径大小,用扫描电子显微镜观察粉末的表面形态。结果制备的鲑鱼降钙素吸入粉末的平均粒径为2.1μm,沉积率在45.42%左右。在pH小于3.3的冰醋酸溶液中,F68的用量超过固型物总量的1%时,喷干温度低于120℃时,鲑鱼降钙素喷雾干燥后的含量均在80%以上。结论在较低的pH环境中,选用适量的蛋白保护剂F68,采用较低的喷干温度,均可有效的降低喷干过程中鲑鱼降钙素的变性几率。

Preparation of salmon calcitonin dry powder inhalation and influential factors of its content

Objective To prepare salmon calcitonin (sCT) dry powders for inhalation by spray-drying method and investigate influential factors of its content. Methods Dry powder inhalations of different pH values and poloxamer contents at various inlet temperatures were prepared. The assay of sCT was proceeded by HPLC. The in vitro deposition properties of the powders were assessed with a twin stage impinger(TSI). The particle size was determined with a laser diffraction size analyzer. Results the aerodynamic diameter was 2.099um and the in vitro deposition rate was 45.42%. The sCT was protected effectively at acetic acid solution of pH 3.0 with 2% of poloxamer at 110℃. Conclusions At a lower pH value and temperature, the degeneration probability of sCT is decreased significantly with suitable protein stabilizer.