Development and Evaluation of Nasal Mucoadhesive in Situ Gel Formulations of Carbamazepine Using In Vitro, Ex-Vivo and In-Vivo Methods

The objective of the present research work was to develop and evaluate the nasal in situ gel formulations of Carbamazepine for better availability in the brain. Mucoadhesive in-situ gelling Carbamazepine formulation were successfully prepared by the spontaneous emulsification method (titration method) using Capmul MCM as the oil, Tween-80 as surfactant, and PEG-600 as co-surfactant phase, 0.5 % (W/W) mucoadhesive in-situ gelling polymer (Deacetylated Gellan gum) on the basis of solubility studies. Formulations were evaluated for gelation study, viscosity study, gel strength, mucoadhesion study, Drug content, permeation study through sheep nasal mucosa, histopathological evaluation of mucosa and pharmacodynamics study in rats, stability study. In-vitro and ex-vivo permeation studies showed an initial burst of drug release at 60 min and in-situ gelling mucoadhesive Carbamazepine formulation show diffusion of 94.30 ±0.01 % drug in 360 min, attributable to the presence of free drug entrapped in the in-situ gelling mucoadhesive layer. In vivo pharmacokinetic studies in rats showed that mucoadhesive in-situ gelling mucoadhesive Carbamazepine enhanced brain and plasma concentrations of Carbamazepine. Histopathological study did not show any damage to the nasal mucosa during permeation. The Anticonvulsants effect of Carbamazepine differed significantly by I.N and I.V routes compared to control. It can be concluded that Carbamazepine given by nasal route is more effective and show quick onset of action when compared to Intravenous administration of equivalent dose.