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BioMed Research International
Volume 2014 (2014), Article ID 847547, 10 pages
http://dx.doi.org/10.1155/2014/847547
Research Article

Formulation and Evaluation of Thermosensitive Biogels for Nose to Brain Delivery of Doxepin

Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India

Received 8 February 2014; Accepted 26 May 2014; Published 18 June 2014

Academic Editor: Kamla Pathak

Copyright © 2014 Anuja Naik and Hema Nair. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Thermoreversible biogels can serve as effective systems for delivery of drugs through nose with increased nasal residence time. The objective of this study was to use chitosan and glycerophosphate based thermoreversible systems for delivery of doxepin to brain through intranasal administration. Formulations were prepared by admixture of suitable dilutions of chitosan and glycerophosphate with or without polyethylene glycol, followed by addition of the antidepressant doxepin hydrochloride. Both systems were evaluated for gelling characteristics, rheology, mucoadhesion, in vitro release, and ex vivo permeation through sheep nasal mucosa. In vivo efficacy was evaluated in Swiss albino mice through the forced swim test. Nasal tissues of mice subjected to repeated exposure to formulation were evaluated histopathologically. Both formulations gelled rapidly at 37°C, returned to sol state on cooling, and exhibited thixotropy. Addition of polyethylene glycol decreased the glycerophosphate content required for gelation and rendered the formulation isotonic. Both gels showed good mucoadhesion, enhanced drug permeation, and provided prolonged in vitro release at 37°C. Efficacy of the formulation in treated groups was inferred from the measured pharmacodynamic parameter and histopathological reports of formulation treated groups showed no significant local toxicity. The biogels could be potential systems for effective drug delivery to brain via nose.