Metered-dose inhaler formulations with beclomethasone-17,21-dipropionate using the ozone friendly propellant R 134a

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.