How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

Abstract

Nasal delivery offers many benefits over other conventional routes of delivery (e.g. oral or intravenous administration). Benefits include, among others, a fast onset of action, non-invasiveness and direct access to the central nervous system. The nasal cavity is not only limited to local application (e.g. rhinosinusitis) but can also provide direct access to other sites in the body (e.g. the central nervous system or systemic circulation). However, both the anatomy and the physiology of the nose impose their own limitations, such as a small volume for delivery or rapid mucociliary clearance. To meet nasal-specific criteria, the formulator has to complete a plethora of tests, in vitro and ex vivo, to assess the efficacy and tolerance of a new drug-delivery system. Moreover, depending on the desired therapeutic effect, the delivery of the drug should target a specific pathway that could potentially be achieved through a modified release of this drug. Therefore, this review focuses on specific techniques that should be performed when a nasal formulation is developed. The review covers both the tests recommended by regulatory agencies (e.g. the Food and Drug Administration) and other complementary experiments frequently performed in the field.

Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

“…A major deviation from this causes irritation of the nasal mucosa. To avoid that, formulation pH should be kept between 4.5 and 6.5 so our formulation satisfies that criterion [48]. The Z-average, PdI and zeta potential values meet the requirements of intranasally administered nanoparticles.…”

Medical devices in allergy practice

“…172 Consequently, in vitro and in vivo studies are required to determine which nasal delivery drug device (NDDD) optimally matches the drug formulation, be it a solution, suspension, emulsion, or powder. 173 In general, NDDD containing topical steroid aerosols are mainly mechanically triggered (pump sprays). Infrequently they can be electrically powered (eg, nebulizer) or gas propellant-driven (eg, atomizer).…”

A consensus research agenda for optimising nasal drug delivery

“…If a consensus can be agreed regarding the most 90 important research questions, then expertise can be combined in collaborative efforts to understand better how to optimize © nasal products. The ideal attributes of a nasal spray are efficient deposition in the nasal cavity, reproducibility, robustness, tolerability and low respirable fraction [11][12][13]. The dependence of nasal deposition on aspects of the spray plume is poorly defined 115 as it is technically difficult to vary properties such as droplet size distribution, droplet velocity and spray cone angle systematically and human factors are also a big influence.…”

“…The critical quality attributes for nasal formulations are not well established, but different pharmacokinetics or clinical outcomes can be influenced by the use of powders versus solutions, different excipients and delivered volume/ mass. A possible strategy to protect the drug from enzymatic 125 degradation may be the forming of protective shells, such as liposomes or micelles, or the addition of enzyme inhibitors and the addition of mucoadhesive agents may enhance absorption by prolonging the residence time of the formulation in the nose [13,14]. For powders, changing the particle size distribution or applying particle engineering can influence deposition and dissolution [12].…”

“…It is still unclear what the impact of dissolution is for current suspension/powder products. A variety of casts have been developed for predicting regional deposition, analogous to the more advanced casts of the throat/lungs that are being used for pulmonary drug delivery [13] and similar questions arise regarding the need for idealized © casts, or casts that reflect sub-populations of patient anatomy or disease. There is little validation of nasal cast models [23], and it has been proposed that biorelevance could be improved by using materials being able to better mimic physiological conditions, such as softer, expandable materials with a flexible nasal valve, or by introducing cells or mucus to reflect the surface characteristics of the nasal mucosa.…”