Particles, dose

Mays CW, Lloyd RD, Taylor GN, et al. 1987. Cancer incidence and lifespan vs. a-particle dose in beagles. Health Phys 52(5) 617-624. 

Many studies present and discuss in vitro and in vivo drug deposition resnlts obtained with inhalation systems. It is often difficult to compare in vitro results from different studies, because different testing equipment and different definitions for the fine particle dose may have been used. 

Wilkes W, Fink J, Dhand R. Selecting an accessory device with a metered-dose inhaler variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler. J Aerosol Med 2001 14(3)251-360. 

Figure 10. Temperature dependence of the number of particles. Dose rate == 0.175 Mrads/hr, water-to-monomer ratio = 2.0...

Holland and Gottfried (1955) studied the changes in density and unitcell dimensions as a function of the total a-particle dose D per milligram of zircon. D was estimated from the present a-activity and the Th/U ratio, together with the age T of the sample, on the assumption that equilibrium in the uranium and thorium decay series had been established in a time that was short compared with T. T was determined from the present a-activity and lead content (see Faure 1977). It was found that for )< 10, the density was approximately 4.7 g/cm. As the dose was increased, the density decreased slowly at first and then more rapidly, and finally approached asymptotically a value of approximately 3.95 g/cm. ... 

Fine particle dose The amount of drug with particle diameter less than 5.0 pm, which is a portion of the inhaled dose... 

Figure 2 Relationship between deposition of a radiolabeled DPI aerosol and the measured fine particle dose of the labeled powder inhaled for each subject. Both variables are expressed as the percent of nominal dose. The correlation is higher for the lower flow rate used to inhale the powder, possibly due to the more consistent amount of drug deposited in the oropharynx. (From Ref. 88.)...

Olsson B, Asking L, Borgstrom L, Bondesson E. Effect of inlet throat on the correlation between measured fine particle dose and lung deposition. In Dalby RN, Byron PR, Farr SJ, eds. Respiratory Drug Delivery V. Buffalo Grove, IL Interpharm Press, 1996 273-281. 

Dose normally ev/gm. Usually calculated from quoted dose to air in same source assuming catalyst absorbs y as does H2O (55.2 x IQi ev/gm H2O, roentgen). Reactor doses frequently given only as integrated flux of neutrons, nvt (density x velocity x time) or cm-2. Charged particle doses sometimes given as flux and time or current and time. 

Figure 3.8 Schematic diagram showing the stmclure of turbulent pipe flow. Forconveniencc, the flow is divided into three regions, Most of the pipe is filled with the turbulent core, with the velocity rising rapidly over the viscous sublayer. The concentration drops more sharply than the velocity because Z3 < V and turbulent dilTusion brings the particles dose to the wall before Brownian diffusion can act etTectively.

Device design often commences with the aerosolisation mechanism, since the fine particle dose reaching the lung is the critical therapeutic dose. This is often a crude mechanism to show proof of principle. However, for regulatory constraints, the metering system is more important, and this is often given insufficient attention in the early stages of a project. 

In optimising the product, both device and formulation are modified, and the normal product release tests are evaluated. Extra investigations are also carried out, such as a standard drop test to ensure that the device is robust. Other major areas for investigation are the dependence of fine particle dose on airflow rate (Srichana et al. 1998), the effect of humidity both on storage (Naini et al. 1998), Maggi et al. 1999) and in-use, drug retention within the device, the effect of orientation and electrostatics (Carter et al. 1998). 

Evans G, Peers A, Sabaliauskas K (2008) Particle dose estimation from frying in residential settings. Indoor Air 18 499-510... 

Fine Particle Fraction and Fine Particle Dose... 

Incorrect handling affects the efficacy of the treatment to a lesser extent than noncompliance. For example, in vitro studies have shown that omission to shake the pMDI before use reduced total and fine particle dose by 25 and 36%, respectively, while two actuations separated by 1 s decreased fine particle dose by 16% (13). The same authors also demonstrated that storing the pMDI stem... 

Nominal dose Metered dose Delivered dose Fine particle dose Retained amount Inhaled dose Exhaled amount Recovered amount ... 

Impaction accounts for most of the large particle trap effect of the spacer. This is illustrated in Fig. 4, which shows the fine and coarse particle doses obtained from a budesonide pMDI (Pulmicort, AstraZeneca, Sweden) actuated into a metal spacer. The spacer was initially 23 cm long, and subsequent reduction in the length of the spacer caused a reduction in both the coarse- and eventually also the fine-particle doses. Even the initial shortening of the spacer reduced the coarse particle dose, whereas the fine-particle dose was unaffected thus, the total particle dose was reduced, but the ratio between fine and coarse particles was improved by shortening the spacer. Thus, the spacer length is critical for the fine-particle dose and the ratio of fine to coarse particles. Different pMDIs have different vapor pressures and therefore different aerosol velocities and volumes as a result, the optimal spacer length is specific to a particular pMDI. Moreover, the spacer should be adapted to the particular aerosol jet. For this reason, the op-... 

The effect of sedimentation was illustrated in an in vitro study in which a budesonide pMDI was delivered through two different spacers, Nebuhaler (Astra Zeneca, Sweden) and Babyhaler (GlaxoWellcome, UK) (Fig. 5). Both spacers are of similar length (200 mm) but have different diameters (80 versus 50 mm) both were primed before use to prevent electrostatic charge effects (see below). The total dose was increased in the wider spacer, mainly due to an increased coarse particle dose, and the half-fife of the fine particle fraction was longer (33 versus 23 s). 

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