A COMPREHENSIVE REVIEW ON FORMULATION AND EVALUATION OF NASAL SPRAY IN-SITU GEL FOR SYSTEMIC AND LOCAL DRUG DELIVERY

Nasal drug delivery offers significant advantages due to the nasal cavity's high vascularization, large surface area, and ability to bypass first-pass metabolism. However, conventional nasal formulations such as drops and sprays are limited by rapid mucociliary clearance, which reduces residence time and bioavailability. Nasal spray in-situ gelling systems represent an innovative approach to overcome this limitation by undergoing sol-gel transition upon exposure to physiological conditions in the nasal cavity. These formulations are administered as low-viscosity solutions that transform into gels triggered by temperature, pH, or ionic composition of the nasal environment. This review comprehensively examines recent advancements in nasal spray in-situ gels for both local and systemic drug delivery. Key polymers including thermoreversible agents (Poloxamer 407/188), pH-sensitive polymers (Carbopol), and ion-sensitive polymers (gellan gum, alginate) are discussed, along with essential formulation components such as mucoadhesive polymers, permeation enhancers, and preservatives. The review elaborates on formulation strategies tailored for local applications (e.g., corticosteroids for allergic rhinitis) and systemic delivery (e.g., peptides, proteins, and small molecules). Critical evaluation parameters including physicochemical characterization, spray characteristics, in vitro drug release, ex vivo permeation, mucoadhesive strength, and in vivo pharmacokinetic and pharmacodynamic studies are detailed. Despite challenges related to device compatibility, mucosal irritancy, dose volume limitations, and scale-up complexities, ongoing research into novel polymers, combination trigger systems, nanocarrier-loaded gels, and nose-to-brain delivery pathways demonstrates immense potential. Nasal spray in-situ gelling systems emerge as a promising platform that combines precise dosing of spray devices with prolonged retention and sustained release, offering enhanced bioavailability and patient compliance for a wide range of therapeutic applications.