Lung deposition variability

Borgstrom, L., Bengtsson, T., Derom, E., and Pauwels, R. (2000), Variability in lung deposition of inhaled drug, within and between asthmatic patients, with a pMDI and a dry powder inhaler, turbuhaler, Int. J. Pharm., 193,227-230. 

The deposition in the mouth is largely due to impaction (except for ultrafine aerosols). This mode of deposition therefore increases with particle size and velocity. The reduction of oropharyngeal deposition is desirable both to improve the efficiency of lung deposition and to reduce its variability [26]. To accomplish this, the velocity of the particles must be sufficiently low. The lower bound for the particle velocity is dictated by the inspiratory flow carrying the aerosol cloud. But some aerosol generators impart high velocity to the particles in the course of formation of the aerosol cloud. 

It can be seen that Newman s approach improves the agreement and results in a slope of approximately 1, but fails to improve variability. Olsson s method on the other hand reduces variability, but it continues to overestimate lung deposition by a factor of 1.7. From the deposition data presented in earlier chapters this overestimate of lung deposition when using FTF would seem quite logical in that none of the deposition models predict complete deposition of this size fraction. It would also be expected that an oropharyngeal model would bring pMDI data more in line with DPI data and reduce scatter since it deals more correctly... 

The data reported in the sections above may, if viewed in a favorable light, lead to the conclusion that there are reasonable correlations between in vitro sizing data and mean lung deposition determined in vivo. (The predictive power of these correlations is discussed in more detail below.) However, one of the other factors that determines the suitability of an inhalation product for use with a particular drug is variability of deposition. As one would perhaps expect a pri-... 

The chapter starts with a brief overview of different principles for dry powder formulation and continues with how the particles are generated at inhalation. Then the importance— for both children and adults—of the intrinsic resistance of an inhaler for the clinical outcome is discussed. Before euumerating the maiketed and also some investigational inhalers, a quick word on the importance of humidity for their performances is given. Finally, lung deposition and its variability is dealt with before the chapter is rounded off by some safety aspects of DPIs. 

The overall delivery of inhaled drugs to the effector site can be described by a number of steps. The variability in lung deposition thus depends on a large number of in vitro and in vivo factors—e.g., device performance, handling of the device, coordination of actuation and inhalation, inhalation flow, patient anatomy, etc. Variability in the different steps will add up to an overall variability in the amount of drug reaching the lungs. 

In vitro analyses are done to ascertain a good quality of the manufactured product and the analyses are done under strictly standardized conditions. The absolute amount of drug leaving the inhaler and its variability are typical in vitro parameters. The in vivo analyses include lung deposition, but also the clinical outcome. The measured in vitro variability may account for only a small portion of the overall in vivo variability observed in the clinical situation. 

The observed difference in variability in lung deposition between Tur-... 

III. Individual Deposition Variability (Nose, Mouth, and Lung)... 

Cuddihy et al. (1978) reviewed a set of experimental data on lung, liver, and skeletal radioactivity after inhalation of 144CeCla by beagles (Boecker and Cuddihy, 1974) to determine the possible range of individual organ burdens in the total population. A second study on variability of aerosol deposition patterns in dogs (Cuddihy and... 

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