Aerosol MMAD

None of the pharmacopeias state any requirements for particle size. However, the particle size specifications set should be appropriate for the intended use of the product. For example, if the particles are intended to reach the deep lung, the MMAD of particles exiting the device should be less than 5 xm. In general, the smaller the aerosol MMAD, the greater the deposition in the lung. 

Wall losses were estimated by comparing the mass concentrations of various elemental constituents of aerosols collected with a series of alternately collected filter and impactor samplers. For samples collected downstream of an electrostatic precipitator (ESP), where the aerosol MMAD was 11.5 pm, the average amount of mass collected in the impactors was about 60% of that collected by the filters (Table... 

Ultrasonic nebulization results in a rise in solution temperature and a decrease in aerosol MMAD with time. The increase in temperature may eliminate the use of this type of nebulizer for the administration of thermolabile drugs to the lung. 

Fig. 1 Transmission (top row) and emission images for the same subject studies with small aerosols (MMAD 3.2 0.2 pm, span 1.8-middle row) and large aerosols (MMAD 6.5 0.2 pm, span 1.7-bottom row). The first three columns are selected coronal slices from the first 2 minute frame of the SPECT study, while the last column represents the corresponding planar images generated from the same SPECT study frame. SPECT PI values were 0.40 and 0.33 for the small and large particle sizes, respectively. Planar PI values were 0.47 and 0.43, respectively, for the small and large particle sizes.

Laube et al. administered a Tc-labeled aerosol (MMAD = 1.12 pm GSD = 2.04), generated by a jet nebulizer, on two different study days to five patients with cystic fibrosis (CF) who had a mean FEVj of 35% of predicted (112). Dis-... 

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). 

Both from deposition studies and force balances it can be derived that the optimum (aerodynamic) particle size lies between 0.5 and 7.5 pm. Within this approximate range many different subranges have been presented as most favourable, e.g. 0.1 to 5 pm [24], 0.5 to 8.0 pm [25], 2 to 7 pm [26] and 1-5 pm [27-29]. Particles of 7.5 pm and larger mainly deposit in the oropharynx [30] whereas most particles smaller than 0.5 pm are exhaled again [31]. All inhalation systems for drug delivery to the respiratory tract produce polydisperse aerosols which can be characterized by their mass median aerodynamic diameter (MMAD) and geometric standard deviation (oq). The MMAD is the particle diameter at 50% of the cumulative mass curve. 

In order to test the validity of the VELUT model it was used to generate predicted isokinetic values of VE differential sampling efficiency for values of MMAD and GSD corresponding to experimental values reported in the literature. A comparison of the experimental data obtained by Carson and Lynch (10) using mono-disperse aerosols of dioctylphthalate, with the predictions of VELUT for the same conditions is given in Table I. This limited data is in excellent agreement with the predictions of VELUT. 

Several groups have investigated the effect of surfactants on emitted droplet size. In the early work performed by Polli et al., the surfactant sorbitan trioleate decreased the MM AD of the CFC dexamethasone suspension when added to the formulation (52). A suspension of terbutaline in a CFC system containing sorbitan trioleate surfactant was shown to have little change in emitted particle size when either 2.8 or 14mg/mL of surfactant was added (53). Interestingly, the surfactant had a significant effect on the obscuration (droplet concentration) of the laser diffraction instrument used to determine particle size. Surfactants may lead to an increase in MMAD due to decreased evaporation rates from aerosol droplets. This may occur because of their tendency to associate at the air liquid interface (54). 

Aerosol particles deposit in the lung by three principal mechanisms inertial impaction gravitational sedimentation and Brownian diffusion. Particles with a larger MMAD are deposited by the first two mechanisms, while smaller particles access the peripheral region of the lung by diffusion. 

The mass median aerodynamic diameter (MMAD) is defined as the aerodynamic diameter which divides the aerosol mass size distribution in half. 

The MMAD and GSD of aerosols are therefore critical factors in determining the deposition patterns within the lung. Aerosols with larger MMADs will deposit higher in the respiratory tract since the aerosol particles will have greater momentum. A polydisperse aerosol is also likely to show greater deposition in the TB region than a monodisperse aerosol of the same MMAD. 

Although they are compact units and hence easily portable, the dense aerosol plume produced often has a population of drops with a higher MMAD and GSD in comparison to air-jet nebulizers and hence ultrasonic nebulizers tend to be less widely used. 

From the plot (Fig. 7.8) an MMAD of 1.2 p.m is found and a ag of 2.0 determined. This is a mass median diameter because the weight or mass of aerosol collected on each stage was used in the analysis. 

Aqueous and ethanolic formulations have been employed with the Respimat and the in vitro aerosol performance determined. Zierenberg (1999) reported fine-particle fractions of 66% for an aqueous fenoterol formulation and 81% for an ethanolic flunisolide formulation. The respective MMADs were 2.0 0.4 pm for the aqueous formulation and 1.0 0.3 pm for the ethanolic formulation [284],... 

We routinely use nose-only inhalation exposure of B(a)P aerosol to evaluate the consequence of prenatal exposure to this toxicant on physiological and behavioral endpoints. The properties of this B(a)P aerosol are shown in Figure 17.4. The aerosol typically exhibits a trimodal distribution with a 93% cumulative mass less than 5.85 pm, 89% cumulative mass less than 10 pm, 55.3% cumulative mass less than 2.5 pm, and 38% less than 1 pm. Fifty-five percent of the aerosol generally has a cumulative mass less than PM2.5 and the mass median aerodynamic diameter (MMAD) + geometric standard deviation for this mode is consistently 1.7 =E 0.085 pm. For several years we employed a rat model exposing timed pregnant dams to inhalation concentrations of 25, 75, and 100 pg/m. ... 

Aerosol properties, such as particle size distribution, aerosol velocity, and hygroscopicity, affect aerosol deposition in the human lungs. Aerosol size distribution, including mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD), is one of the most important variables in governing the site of droplet or particle deposition in the lungs. ... 

Fig. 15 shows the drug mass recovered from the various stages of the impactor and device at a nominal drug dose of 75 pg per actuation. The amount of drug deposited on each stage was used to calculate the MMAD and GSD. The calculated MMAD was 2.85 pm with a GSD of 1.6. The fine particle fraction (FPF) of the aerosol was 90% (<5.8 pm) of the emitted dose, and 95% (<5.8 pm) of the dose distal to the USP throat. 

Inhalation of an extrafine aerosol (< 1 pm MMAD) of Technegas, 99mtechnetium (99mTc) sulfide colloid or albumin... 

Most MDIs contain surfactant materials that might be expected to affect growth. The shift in size distribution caused by exposure of MDI-produced aerosols to high (95-96%) humidity is modest. The MMAD of a metaproterenol sulfate aerosol from an MDI increased from 4.05 pm at 16% relative humidity to 5.22 pm at 98% relative humidity [23], and similar studies indicate growth also for sodium cromolyn [25], The high humidity used in these studies was not as high as the 99.5% humidity present in distal lung [26],... 

The second study was a double-blinded comparative trial of secondary prophylaxis comparing 60 mg aerosolized pentamidine given every 2 wk after five weekly loading bases to placebo using a handheld FisoNeb ultrasonic nebulizer with a 5- xm MMAD particle size [36,37], The study was intended to run 6 mo, but it was terminated early, with a mean follow-up of only 3.7 mo. Aerosolized pentamidine significantly reduced the reoccurrence rate of PCP as compared to controls in this study [37,38]. 

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