Non-volatile Excipient effect on Inhaled Drug Product Performance

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Summary

Pressurised metered dose inhalers containing varying ratios between non-volatile excipient and beclomethasone dipropionate (BDP) have been formulated to have similar stage deposition patterns and statistically similar aerosol characteristics. With the formulations being size-equivalent, differences in dissolution profiles can be attributable to the influence of the non-volatile excipient (NvE). The dissolution profiles suggest that BDP dissolution rate is reduced with increasing amount of excipient in the formulation. Time taken for 25% of drug to be released, T25 in glycerol-containing formulations in order of increasing excipient content was 33.6 mins,101.9 mins, 75.7 mins, 150.9 mins, and 119.9 mins for A to E respectively. T25 for isopropyl myristate (IPM) formulations was 8.9 mins, 16.0 mins, 54.1 mins, 44.6 mins and 57.7 mins for F to J respectively. The reason for the faster dissolution of IPM-containing BDP formulations compared to glycerol formulations is not clear but may be a result of a solubilising effect of IPM on BDP. This study provides insight into the effects that non-volatile excipients may have on aerosols produced by solution pMDI, their dissolution and how this may impact on BDP pharmacokinetics