The formulation and evaluation of a CFC-free budesonide pressurised metered dose inhaler

Although dry powder inhalers are well established for the delivery of corticosteroids, the pressurised metered dose inhaler remains the preferred and most cost effective presentation. To design an HFA solution formulation which matched marketed CFC products (Pulmicort and Desonac DA) two elements of the Chiesi Modulite system, the addition of a non-volatile component and the actuator orifice diameter, were varied. These variables, which were shown by in vitro tests to influence the fine particle dose and its mean particle size in different ways, could be permuted to give an aerosol cloud with size characteristics very close to the comparator products. The likelihood that this would confer clinical equivalence is reinforced by a pharmacokinetic analysis which showed that the chosen HFA solution formula gave similar systemic absorption from the lung as Pulmicort. The equivalence in aerosol characteristics was sustained when the pressurised metered dose inhalers (pMDIs) were used with spacers. The Chiesi Jet and the AstraZeneca Nebuhaler, when used with their respective pMDIs, reduced likely oropharyngeal deposition to the same extent and gave a similar increase in the fine particle dose.