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and powder forms. Various technical approaches in devices have been used to provide options for preserva- tive-free formulations including anti-bacterial compo- nents (e.g., silver), mechanical tip closures with micro- bial filters and so-called "bag-on-valve" technologies. The potential of unit-dose and bidose nasal delivery devices Common features Unit dose (single dose) or bidose (dual dose) drug deliv- ery spray devices come in many forms but tend to have common characteristics such as: • An unpreserved, pre-filled liquid or powder dose in a protective chamber • Some means of delivering and atomizing the liquid dose or a pre-prepared powder formulation with a particle size suitable for effective nasal dosing • Usually disposable after usage of one or two doses Potential benefits Unit dose and bidose forms can be less complicated to develop than multidose systems. They can also readily be customized for product differentiation, e.g., Zomig ® (zolmitriptan) (AstraZeneca) and Subsys ® (fentanyl sub- lingual spray) (Insys Therapeutics). Figures 1-4 show examples of available technologies for unit dose and bidose nasal delivery. In addition, the industrial filling and packaging pro- cesses used in their manufacture are well established and have been validated, often with off-the-shelf or mini- mally customized equipment being employed. These dosage forms can offer a variety of benefits includ- ing sterility and "ready for use" in cases of emergency treatment. They generally contain smaller amounts of drug/formulation than multidose units, which may increase their safety and decrease the risk of diversion issues related to controlled substances. These devices can also provide convenience to patients because they tend to be small, portable and ready for use without the requirement for priming. These character- istics can also aid patient adherence because device use can readily be monitored and doses can easily be counted, while with multidose systems, dose counters may not be readily available so dose monitoring can be more challenging. Regulatory and human factors expectations The technical and regulatory expectations for nasal and sublingual sprays have evolved and been clarified over the last few years in both Europe and the United States 7-10 with other regions such as South America following rapidly. Parameters such as droplet or particle size distri- bution, spray pattern, dose content uniformity and extractable and leachable profiles are now common expectations for regulatory dossiers. Consequently, drug delivery devices, as well as their corresponding formula- tions, have evolved to meet the increased requirements of specifications and quality standards. Today's regulatory requirements also expect that drug delivery devices undergo human factor analysis (HFA) 10 Figure 3 A bidose powder device Figure 4 A bidose liquid device Inhalation JUNE 2016 13 (Photo enlarged to show detail) (Photo enlarged to show detail)