Development of a physiologically relevant method for nasal spray analysis using simulated nasal mucus

Objectives. Current methods for testing nasal spray dosage forms during development fail to fully assess the behavior of the drug following its release from the container, including subsequent distribution, retention, and permeability across the mucosal barrier. Existing in vitro models typically overlook the critical factor of drug interaction with nasal mucus, which substantially limits their predictive power and physiological relevance. The study set out to develop a physiologically based analytical method that addresses this gap by employing representative simulated nasal mucus compositions to evaluate the key performance parameters of the spray.

Methods. The pH of the investigated compositions was determined potentiometrically in accordance with the requirements of the 15th Russian State Pharmacopoeia, OFS.1.2.3.0032, using a pH meter (Econix-Expert, Russia) equipped with an ESK-10601 glass electrode (Izmeritelnaya Tekhnika, Russia). The dynamic viscosity of the compositions was measured using a Brookfield DV2T RV rotational viscometer (Brookfield, USA) with a thermostatically controlled measuring unit ofthe coaxial cylinder type within a temperature range of 25–37°C. The contact angle was determined by the sessile drop method using an EasyDrop Standard instrument (Krüss, Germany). The distribution of nasal sprays was evaluated with a silicone model of the human nasal cavity (Koken Co. Ltd., Japan).

Results. Representative simulated nasal mucus compositions were developed and characterized that reliably reproduce the key physicochemical and rheological properties of human nasal secretions under both normal and pathologically inflamed conditions. An experimental setup combining an anatomical silicone nasal cavity model with an applied layer of simulated nasal mucus was created and validated. The developed model permits quantitative assessment of key parameters, such as the distribution and coverage area of the drug substance upon contact with mucus of varying viscosity. As such, it provides a physiologically relevant platform for studying nasal sprays during dosage form development.

Conclusions. The proposed approach offers a valuable tool for optimizing the composition and design of nasal sprays, enabling comparative analysis under conditions that closely mimic physiological realities.

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