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Inhalation JUNE 2017 11 mesh is not cleaned according to manufacturer instruc- tions. 17 When developing suspension formulations for nebulization, it is important to consider the size of the drug particles that make up the suspension. Given most drug particles are asymmetric in shape, it is the size along the smallest axis that is most critical. Therefore, suspen- sions of budesonide are able to be used successfully with many mesh nebulizers despite having a volume equiva- lent diameter similar to that of the nozzle due to their asymmetric shape. Continuity of care can be accomplished by using the same mesh aerosol generator to fit both the ventilator circuit and an add-on aerosol holding chamber, with mask or mouthpiece, for use in the emergency room and in a portable nebulizer at home. 18 Thus, within the mar- ket for nebulizers, market research reports show that sales of mesh nebulizers are expected to grow faster than jet and ultrasonic types of nebulizer. 19 Nebulizers in the development process From a pharmaceutical perspective, formulation of a new drug for nebulization is relatively straightforward, with addition of surfactants to stabilize a suspension if the drug is insufficiently soluble to form a stable solu- tion. This can either be provided in bulk, as for hospital use, or as individual doses, usually in a blow-fill-seal con- tainer. However, it does require manufacture under aseptic conditions, which will add to the manufacturing complexity. Alternatively, the drug can be supplied as a unit dose dry powder for reconstitution with water before use. The relative simplicity with which a liquid formulation can be developed means it can be created rapidly and with minimal amount of drug substance, when the drug is at its most expensive to produce. This is in contrast to a pMDI or DPI inhaler, which will require formulation of inhalable particles with the pro- pellant/carrier and demonstration of pharmaceutical performance of the drug delivered by the inhaler. Fur- thermore, inhalers need to be shown to maintain perfor- mance at end-of-shelf-life before going into a clinical trial, whereas nebulized formulations only require phys- ical and chemical stability of the formulation to be demonstrated. Many nebulizers can be used with up to 8 mL of liquid, which makes them particularly suitable to administer high doses of drug during the early stages of clinical development, when the maximum tolerated dose needs to be established. This is because the devices are designed to operate with normal tidal breathing so patients tend not to tire if the size of the dose requires treatment times in excess of 10 minutes. At the other end of the scale, there are small volume (50-300 µL) mesh devices in development that, for drugs that can be for- mulated in concentrated form, can deliver a dose in one to six breaths, thereby simulating inhaler delivery, but with the advantages of a liquid formulation. 20 Furthermore, mesh nebulizers/devices are particularly suited to the delivery of macromolecules, as they subject the formulation to relatively low shear, liquid passes through the orifice only once and there is no heating of the formulation. These factors combine to retain the er tt be -C AR A ST er t designs fas er v CCM+: Disco truction is af an obs y a w s air ' patient es s. In r vior beha clinical decisions b -CCM+ can be used t AR A S application of numer ving h o pr Im er tt be T hing. eat ecting br f s af w o ho viding insight int o ed, pr can be simulat he hin t w wit he flo y medicine, t or at pir omatic t p o sym y insight int e viding k o y pr s b icult f s in making dif or t doct sis o as be used t ical diagnosis. of numer he ough t hr e t hcar healt . er t designs, fas siemens.com/mdx