Introduction and objectives The particle size distribution and the median mass aerodynamic diameter (MMAD) of an inhaled product are important characteristics which may influence the deposition of the drug in the lung and as a consequence may also affect its therapeutic index. We evaluated the relationship between in vitro MMAD and in vivo lung deposition (LD, expressed as fraction of the delivered dose) and the exhaled fraction (EF), using relevant literature from scintigraphic studies conducted in healthy volunteers and asthmatic patients. Moreover the relationship between the ratio of EF to LD and MMAD has been further assessed.
Methods Data from 21 studies in healthy volunteers (15 with pressurised metered dose inhalers (pMDI) and 6 with dry powder inhalers (DPI)) and 11 studies in asthmatic patients (8 pMDI and 3 DPI) have been evaluated. Asthmatic patients had a FEV1 >70% predicted, supporting pooling of the data with that of healthy volunteers.
Results LD increased when MMAD decreased, so that when MMAD is about 1 µm the LD is more than 50%of the delivered dose and becomes markedly lower when MMAD approach 4 µm. EF is low and did not change markedly. On the contrary, the ratio EF/LD is independent of the MMAD, suggesting that the EF is proportional to the LD and not affected by MMAD.
Conclusion These data demonstrate that the EF/LD ratio is independent from the MMAD providing reassurance that a smaller particle size will not be associated with a higher exhaled fraction.