DIFFERENCES IN AERODYNAMIC PARTICLE-SIZE DISTRIBUTIONS OF INNOVATOR AND GENERIC BECLOMETHASONE DIPROPIONATE AEROSOLS USED WITH AND WITHOUT A LARGE-VOLUME SPACER

Background - The equivalence of generic beclomethasone dipropionate (BDP) formulations with their innovator counterpart must be demonstrated if generic formulations ape to be used. This study has examined the aerodynamic particle size distributions of both innovator and generic formulations of BDP and the effect of a large volume spacer (Volumatic) on these distributions. Methods - Aerosol clouds of three formulations of BDP delivering 250 mu g per metered dose were characterised using a high precision multistage liquid impinger, and the amount of drug in different particle size bands was determined by spectrophotometric assay. Results - The mean (SD) respirable fractions of Becloforte, Beclazone, and Filair without the spacer (n=10) were 24.1 (2.1)%, 23.1 (2.7)%, and 23.0 (2.1)% respectively; however, the ratio of deposition on stage 4 of the impinger to that on stage 3 was lower for Beclazone and for Filair than for Becloforte, implying a smaller proportion of fine particles for the generic products. When the three products delivered via the Volumatic spacer device were compared, the respirable fraction for Becloforte (n=10) was 25.0 (4.0)%, but those of Beclazone (n=10) and Filair (n=11) were 16.0 (1.9)% and 14.6 (3.4)%. Repeat testing (n=5) at a later date showed higher mean respirable fractions for all three products, but a trend towards the highest respirable fraction for Becloforte, and the same rank order for the other two products. Conclusions - These in vitro findings suggest that the particle size distributions of the two generic formulations of BDP are not equivalent to that of the innovator product. Some differences in particle size distributions might not have been detected by a twin impinger. Clinical testing would be required to assess the therapeutic equivalence of innovator and generic corticosteroid products used with or without spacer devices.