Therapeutic aerosols, distribution

M Dolovich. Lung dose, distribution, and clinical response to therapeutic aerosols. Aerosol Sci Technol 18 230-240, 1993. 

Because the therapeutic aerosols frequently have a log-normal type of size distribution, polydispersity usually implies that there is a long tail of particles with large aerodynamic diameters. These big particles contain a significant fraction of the therapeutic dose. Several theoretical calculations indicate that there should be very significant differences in the regional deposition of aerosols with the degree of polydispersity found in conventional therapeutic aerosols compared to the deposition of monodisperse aerosols [50,57-61]. A reduction in alveolar deposition from about 60% of the inhaled dose to less than 30% was... 

The MMAD is a parameter frequently used to characterise therapeutic aerosols. MMAD alone is not very useful however, as it provides no information about the size distribution in the aerosol and the mass fraction of the dose (label claim) processed into a suitable aerosol. Fine particle dose and fraction are more meaningful parameters, particularly for DPIs (see definitions). 

MMAD is frequently presented as the parameter characterising aerosols from inhalation devices best. This is not true however. To judge the quality of a therapeutic aerosol from a particular type of inhaler, more information is needed. The MMAD does not give any information about the size distribution of the aerosol particles. Substantial mass fractions may be outside the desired size range for adequate deposition of active substance in the target area, even when MMAD looks very favourable. Moreover, MMAD does not give information about the mass fraction of the dose (label claim) that has been delivered within the desired size range. For aU types of inhalers, the delivered fine particle dose (FPD) is much lower than the label claim and this may vary from 10 % to 60 % for DPIs and up to 90 % for... 

Figure 6.20. The Aero-Disperser attachment for the Aerosizer , enables aerosol preparation at controlled shear rates, a) Internal structure of the AeroDisperser. b) The effect of various shear rates can be seen from the size distributions generated for a pharmaceutical powder intended for use as a therapeutic aerosol.

Swift DL. Use of mathematical aerosol deposition models in predicting the distribution of inhaled therapeutic aerosols. In Hickey A, ed. Inhalation Aerosols Physical and Biological Basis for Therapy. New York Marcel Dekker, 1996 51-81. 

Most product information leaflets for nebulised medicine formulations discourage mixing of marketed formulations but in practice different formulations are frequently mixed to increase patient comfort. Particularly CF patients tend to combine medicines in order to save time as well as to overcome adverse effects (e.g. bronchoconstriction) of one active substance (antibiotic) by another (salbutamol). They also tend to refill their nebuliser with a new medicine without emptying and cleaning the nebuliser between the administrations. Relatively little has been reported in the literature about the compatibility of medicine mixtures, however, and interactions may be expected with respect to chemical and physical stability, droplet size distribution of the aerosol, nebuliser output rate and therapeutic effect. From a survey of studies on chemical stability, it is known that particularly domase alpha (Pulmozyme ) is incompatible with many other nebulised medicine formulations due to inactivation of the protein [63]. Additives, like stabilisers that work well in some medicine formulations, may be incompatible with other preparations and induce cloudiness... 

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