Targeting by Size Control

The goal of most manufacturers has been to produce particles in the 2- to 3-mm size range, although this is not always achieved. This size seems most appropriate for delivering the greatest mass to small airways. Based on information about b2-adrenergic receptor location, this is the proper area to target for treating asthma. Examination of plots of regional deposition indicates that 20-30% of particles of this size will deposit in the airways during normal breathing. Although ultrafine particles, those smaller than 0.1 mm, deposit in distal airways in progressively greater fractional quantities, the mass of 0.03- and 0.3-mm particles is, respectively, 10"6 and 10"3 that of a 3-mm particles. An aerosol of ultrafine particles needs to be much more concentrated or inhaled much longer to deliver an equivalent mass of drug. Such a particle concentration cannot be practically achieved. Consequently the 2- to 3-mm size is the most practical for best overall respiratory tract dosing. This size is also effective for delivering the greatest total mass to the pulmonary region. Traditional aerosols deliver heterodisperse aerosols, so if the size is stated as 3 mm, this in fact represents the mass median aerodynamic diameter (MMAD). Many particles are smaller and many larger. Knowledge of this distribution allows calculation of estimated deposition parameters based on lung models. If the size distribution can be narrowed, the aerosol can be targeted somewhat more tightly, and efficacy for a given dose may change. There is some evidence for this. Administration of ipratropium bromide, 8 mg, as a monodisperse 2.8-mm aerosol is as effective as administration of 40 mg as a heterodisperse aerosol from a metered-dose inhaler (MDI) and spacer [17]. In practice, standard medical devices cannot generate monodisperse aerosols.

Size can be controlled by many aspects of aerosol generation. These include control of hygroscopic growth, control of evaporation, and control of generation techniques. While manipulation of particle growth characteristics is not commonly studied, it has some potential as a means of aiding targeting. Control of generation and inhalation techniques are usually given more attention, and such will be our approach.

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Dealing With Asthma Naturally

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