Steckel H, Müller B W
Christian-Albrecht-University Kiel, Germany.
Eur J Pharm Biopharm. 1998 Jul;46(1):77-83. doi: 10.1016/s0939-6411(97)00115-x.
Metered-dose inhalers (MDI) are the most widely prescribed devices in the treatment of lung diseases but the continued use of chlorofluorocarbons (CFC) as propellants has made them unpopular due to their influence on the stratospheric ozone layer. The purpose of this study was to show possibilities of formulating beclomethasone-17,21-dipropionate (BDP) with the alternative propellant R 134a as a solution or as a suspension-type metered-dose inhaler. Influencing factors such as surfactant concentration, cosolvent content and actuator tube design were investigated. Metered-dose inhaler formulations were manufactured using a pressure filling technique. The resulting formulations were characterized with regard to their emitted fine particle fraction using the two-stage impinger, BP 93. Fine particle fraction was found to be independent on the surfactant concentration but highly dependent on the cosolvent content and the actuator tube design. In vitro fine particle fractions of 50% were obtained with solution phase MDIs. Formulating BDP as a suspension resulted in unstable dispersions in most cases because of the partial solubility of the drug in the liquified propellant. Stable suspension formulations gave an in vitro fine particle fraction of about 30%. A comparison with established marketed BDP suspension formulations which were found to emit a fine particle fraction in the range 10-50% showed the equivalence of the new CFC-free formulations.
定量吸入器（MDI）是治疗肺部疾病时处方最广泛的器械，但由于其对平流层臭氧层的影响，继续使用氯氟烃（CFC）作为推进剂使其不受欢迎。本研究的目的是展示用替代推进剂R 134a将丙酸倍氯米松-17,21-二丙酸酯（BDP）配制成溶液或混悬型定量吸入器的可能性。研究了诸如表面活性剂浓度、助溶剂含量和雾化器管设计等影响因素。定量吸入器制剂采用压力灌装技术制备。使用两级冲击器（BP 93）对所得制剂的细颗粒喷出比例进行了表征。发现细颗粒比例与表面活性剂浓度无关，但高度依赖于助溶剂含量和雾化器管设计。溶液相定量吸入器的体外细颗粒比例可达50%。在大多数情况下，将BDP配制成混悬液会导致分散体不稳定，因为药物在液化推进剂中有部分溶解度。稳定的混悬液制剂的体外细颗粒比例约为30%。与已上市的BDP混悬液制剂（细颗粒喷出比例在10%-50%之间）的比较表明，新的无氯氟烃制剂具有等效性。
