Physiological Pharmaceutics

236 Physiological Pharmaceuticsproblems. Unfortunately most nebulizers are bulky and require a fixed power source, whichlimits their use severely.In order to combine these advantages of nebulizers with the portability of MDIs,Boehringer Ingelheim have developed the Respimat ® , a spring-driven spray with a similaroutward appearance to a conventional MDI. Unlike an MDI, the Respimat ® delivers itsspray in a slow low-velocity cloud. This leads to increased central pulmonary deposition 14 ,which is probably due to the increased time available for droplet evaporation beforeinhalation, and the reduced plume velocity, which reduces oropharyngeal impaction. Sincethese two factors are the main reasons for the success of spacer devices (see below), theaddition of a spacer to a Respimat ® caused no significant improvement in deposition.Spacer devices and ancillary equipmentA number of techniques have been used in an attempt to improve the deposition of inhaleddrug particles. The best known of these are the various kinds of spacers, chambers whichare placed between the inhaler device and the patient’s mouth (Figure 10.9). These devicescause considerable improvements in the fraction of dose deposited in the lungs and operatethrough a number of mechanisms. Firstly they provide a delay time before inhalation toallow full evaporation of propellant, so that the particles have reached their minimum size.Secondly they slow down the particle cloud so that the impaction velocity on theoropharynx is reduced, thus reducing impaction in this region. Finally they have a reservoirfunction which makes the timing of inhalation by the patient less critical. A typical exampleof such a device is the Nebuhaler ® , which was studied by Thorsson et al for the delivery ofbudenoside. The Nebuhaler ® caused a significant increase (from 12% to 38%) inpulmonary deposition, and an improvement in peripheral deposition. When assessingstudies of such devices, it is important to realize that the spacer itself acts as an impactionfilter and a proportion of the larger droplets are removed by it. In addition plastic devicesaccumulate wall charges and act as electrostatic precipitators, causing significant drug losseswhich vary with handling, humidity and cleaning or priming history 15 .Several methods have been developed to fire the aerosol device when the patient’sbreathing is correctly timed. We have already mentioned the Autohaler ® which is fired bya pressure switch. More recent devices such as the SmartMist ® and AERx ® add thesophistication of microprocessor control so that usage can be logged and the device can becontrolled with a degree of sophistication 16 17 .Figure 10.9 A typical spacer device