Intranasal Dry Powders as Dosage Forms: Formulation Aspects and Pharmacokinetic Evaluation Techniques

Intranasal dry powder dosage forms have attracted interest in the last decade due to their advantages over liquid nasal dosage forms. These advantages include increased residence time in the nasal cavity, greater chemical stability and improved bioavailability for some drugs. Particle properties (e.g., particle size and morphology) of intranasal dry powder formulations play a vital role in the aerodynamic behaviour and consequently the deposition site of particles in the nasal cavity, which impacts drug delivery efficiency. Furthermore, the device used to administer the intranasal dry powder should be carefully selected, as it can influence particle deposition and ultimately therapeutic outcome. Certain challenges exist when evaluating the pharmacokinetic properties of intranasal dry powder formulations using in vitro and ex vivo models, such as uneven coverage of the epithelial surface and maintenance of membrane integrity. Furthermore, due to anatomical differences, some in vivo animal models may overestimate the drug delivery performance of intranasally administered dry powders (especially nose-to-brain drug delivery) and therefore have limited translational value. Although regulatory criteria for intranasal dry powders are available, specific and harmonised guidance on the formulation and evaluation of these dosage forms is still lacking. This review provides insights into key aspects of intranasal dry powder dosage forms, including formulation aspects, particle engineering strategies, the role of dry powder delivery devices, regulatory aspects and models available for the evaluation of the pharmacokinetic properties of intranasal dry powder dosage forms.