Vahid Vikram Minglani, Meenakshi B Patel, Tarun Kumar Upadhyay
The optimized nanoemulsion-based in situ gel demonstrated sustained drug release, enhanced nasal permeation, acceptable safety, and improved antidepressant efficacy. These findings indicate that the developed formulation is a promising non-invasive platform for intranasal delivery of escitalopram oxalate with the potential to enhance nose-to-brain delivery for depression therapy.
BACKGROUND: Escitalopram oxalate is a Biopharmaceutics Classification System (BCS) Class II drug with low aqueous solubility and significant first-pass metabolism, limiting its systemic bioavailability and therapeutic efficiency. Intranasal delivery using a nanoemulsion-based thermosensitive in situ gelling system offers a promising strategy to bypass first-pass metabolism, improve drug solubility, prolong nasal residence time, and facilitate nose-to-brain drug delivery.
OBJECTIVE: This study aimed to develop and optimize a nanoemulsion-based in situ gel for the intranasal delivery of escitalopram oxalate to improve drug delivery and antidepressant efficacy.
METHODS: Escitalopram-loaded nanoemulsions were prepared by high-energy emulsification using a hybrid oil phase of arachis oil and Caproyl 90 (1:1), Tween 80 as the surfactant, and PEG 400 as the cosurfactant. Formulations were optimized using a Central Composite Design (CCD) and characterized for droplet size, polydispersity index (PDI), zeta potential, drug content, gelation temperature, pH, viscosity, spray characteristics, in vitro drug release, ex vivo nasal permeation, nasal ciliotoxicity, RPMI 2650 cell viability, and pharmacodynamic activity in Wistar rats.
RESULTS: The optimized formulation exhibited a droplet size of 34.93 nm, PDI of 0.1955, zeta potential of - 38.4 mV, 97% drug content, pH of 6.4 ± 0.93, and a gelation temperature of 34 ± 1 °C. The formulation demonstrated sustained drug release over 8 h, significantly enhanced ex vivo nasal permeation compared with the nanoemulsion alone, uniform spray performance, and an acceptable safety profile in nasal ciliotoxicity and RPMI 2650 cell viability studies. Pharmacodynamic evaluation showed significantly greater reduction in depressive-like behaviours than oral escitalopram solution.
CONCLUSION: The optimized nanoemulsion-based in situ gel demonstrated sustained drug release, enhanced nasal permeation, acceptable safety, and improved antidepressant efficacy. These findings indicate that the developed formulation is a promising non-invasive platform for intranasal delivery of escitalopram oxalate with the potential to enhance nose-to-brain delivery for depression therapy.