Nebulizers

Nebulizer formulation conforms to sterile product preparation, which means that drug stability in solution in the presence of additives must be evaluated. Historically, it was sufficient to use antimicrobial agents in the formulation, notably benzalkonium chloride. Adding antimicrobials is not considered now an acceptable approach to the formulation of nebulizer solutions. The solubility of the drug is important since it may impact on the performance of the solution in a selected nebulizer. Additives may form complexes with the drug.

Components include an energy source (gaseous, electrical), a site of energy input to solution (capillary tubes, piezoelectric plate), a means of removing large droplets (baffle plate), and tubing and a face mask to deliver aerosol.

Hook region

Aerosol

Baffle

Drug solution

Compressed air

Aerosol

Baffle

Hook region

Compressed air m

Figure 8 (A) Droplet formation. (B) Droplet delivery from an air-blast nebulizer.

Drug solution

The mechanisms of delivery are either air-blast or air-jet and ultrasonic systems. The theory for each of these mechanisms has been elucidated to the same degree.

Droplet delivery from an air-blast nebulizer is governed by the surface tension, density, and viscosity of the fluid, and the applied pressure, which can be passive or forced. Droplet breakup is illustrated in Figure 8. Droplets form during this breakup at a critical Weber number (We).

Cd where CD is the coefficient of discharge, and

where pA is the air density, t/R the velocity, D the diameter of the nozzle, and rj the liquid viscosity.

Droplets are dispersed from nebulizer nozzles by one of five basic mechanisms based on Bernoulli (Venturi) effect. There are two categories of arrangement of liquid feed supply with respect to the driving gas supply: separate liquid and air feed nozzles and coaxial nozzles. The latter coaxial arrangement has four potential orientations: central gas with internal mixing, central gas with external mixing, central liquid with internal mixing, and central liquid with external mixing. The high-pressure airstream passes over or around the liquid feed nozzle, inducing a low-pressure region, which draws solution through a capillary. The liquid is subsequently dispersed in the air.

Performance of nebulizers is not measured in the same manner as pMDIs and DPIs. Since the drug solution is not supplied with the device, the time scale of compatibility is much smaller. Droplet size and distribution and dose delivery are, however, very important.

The manifestation of through-life evaluation, which is important to these devices, is the delivery of a single dose. The emitted dose and droplet size may vary from the beginning to the end of the delivery period.

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