Hemanth Kumar Mamidi, Madhavi Harika Srimathkandala, Krishna Sanka, Madhu Babu Ananthula, Vasudha Bakshi The objective of the present research work was to develop and evaluate the nasal in situe gel formulations of alprazolam for better availability in the brain. Formulations were developed using Pluronic F127 and sodium alginate by cold method. Formulations were evaluated for permeation study through sheep nasal mucosa, histopathological evaluation of mucosa and pharmacodynamic study in rats. Optimized formulation showed a diffusion of 78.75 ± 0.077 % drug in 240 min, effective permeation coefficient (Peff) and gelling temperature were found to be 6.44×10-5 cm sec-1 and 33.80 ± 0.57°C respectively. Histopathological study did not show any damage to the nasal mucosa during permeation. The locomotor activity and anti-anxiety effect of Alprazolam differed significantly by I.N and I.V routes compared to control. It can be concluded that Alprazolam given by nasal route is more effective and show quick onset of action when compared to Intravenous administration of equivalent dose. International Journal Of Pharmacy 2249-1848 2015-01-02 1 278-288 Copyright (c) Pharma Scholars. All rights reserved 2013