Development of nasal pharmaceutical products for systemic exposure: use of permeation enhancers to achieve target product profile

In recent years, special attention has been paid to non-invasive parenteral routes of administration, which are an alternative to injectable drugs, as well as other dosage forms whose effectiveness and safety may be compromised by the administration route. At the same time, there is a paradigm shift in relation to nasal dosage forms: they are no longer considered as primarily drugs exhibiting local effects, and an increasing number of nasal medicinal products with systemic action are appearing on the market. There is a growing interest to the nasal delivery due to the possibility of maximizing the therapeutic potential of active substances that have proven themselves in clinical practice, for example, by quick targeted action to the site of the pathological process, increased bioavailability of the drug and reduced possible side effects. The nasal cavity as a site for systemic drug absorption has anatomical and physiological features that include a relatively large surface area, a porous endothelial basement membrane, a highly vascularized epithelial layer, high total blood flow, lack of first-pass metabolism, and easy access. Therefore, the development of a convenient (nasal) dosage form of the drug with a rapid onset of action is a promising approach. When developing a new pharmaceutical product, the factors that determine bioavailability should be taken into account and addressed by appropriate formulation and delivery techniques: the use of mucoadhesive components or substances that modulate mucociliary clearance, variation of the viscosity or osmolarity, or selection of an appropriate dosing device. Improving intranasal absorption is a promising direction for obtaining drugs with improved consumer properties. In addition to the functional properties of the formulations, safety aspects must also be taken into account. The article provides an analysis of the limiting factors for nasal preparations, strategies for increasing bioavailability, permeation enhancement mechanisms, and provides examples of the application of permeation enhancers used in developed and commercially available drugs. This review gives an idea on possible to use in nasal formulations permeation enhancers which have different mode of actions.