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

Arun B. M.*, Ganesh Raghunath Nayak, A. R. Shabaraya

ABSTRACT

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.

Keywords: Nasal drug delivery; in-situ gel; mucociliary clearance; sol-gel transition; thermoreversible polymers, systemic delivery; local delivery; bioavailability; sustained release; permeation enhancers; nose-to-brain delivery.