DPIs allow the administration of high-dose antibiotics. Most DPI devices are in portable sizes and convenient to carry (Zhou et al. 2014c). Drugs and excipients are present in a powder form, which is generally more stable than solutions or suspensions. Administration of DPI can be achieved within 1-2 min. These advantages provide superior patient compliance as exemplified by CMS and tobramycin DPIs (Geller et al. 2007). Passive DPI devices require the inspiration airflow generated by the patients to aerosolize the powder and thus are not suitable to deliver powder aerosols to infants and incubated patients. Recently, a novel powder aerosol system has been developed to administer high doses (up to 320 mg) of mannitol powder from a passive DPI to the distal end of tracheal tubes in critically ill patients (Tang et al. 2011, Chan et al. 2012) (Figure 7.1).
Only one antibiotic DPI of tobramycin (TOBI® Podhaler®) has been approved in the United States. DPI of CMS (Colobreathe®) was only approved in Europe. Two more (ciprofloxacin and vancomycin) are in the advanced development stage (Table 7.2). Both approved antibiotic DPIs of TOBI Podhaler and Colobreathe are using single-dose reloadable capsule-based devices with drug powders packaged and stored separately. Multidose inhalers are not suitable for high-dose antibiotics because accommodating a large amount of powder inside the inhaler would make the device too bulky to handle. In Colobreathe, each capsule contains 125 mg of colistimethate sodium powder. A single inhalation may not complete the dose; multiple inhalations are often needed. In TOBI Podhaler, 28 mg of drug is prefilled in a capsule and four capsules are administrated sequentially (112 mg per dose). One concern on the usage of this product is that it requires repeating procedures for four capsules, which is an onerous process for patients with a higher risk of misuse. Another device, Orbital® inhaler, could also deliver 200 mg of powder by multiple inhalations. High emitted
FIGURE 7.1 Experimental setup to determine the dose and particle size distribution of mannitol aerosol coming out from the tracheal tube via a novel powder aerosol delivery system designed for the incubated patients. (Reprinted from Tang, P. et al., J. Aerosol Med. Pulmon. Drug Deliv, 24(1), 1, 2011. With permission from Mary Ann Liebert, Inc.)
doses (>90%) were obtained within <10 inhalations for the spray-dried ciprofloxacin or mannitol powders (Young et al. 2014). In addition, single-use disposable devices have been developed for antibiotics. Twincer® is a disposable device used to deliver colistin for CF patients and has potential also for antituberculosis formulations. It has only three simple parts and can be easily assembled. A multiple air classifier technology is built in the Twincer for powder dispersion (de Boer et al. 2006).