DEVELOPMENT OF MUCOADHESIVE NASAL IN SITU GEL TO SUSTAIN THE RELEASE OF AMITRIPTYLINE HYDROCHLORIDE
Amitriptyline is a tricyclic antidepressant. It has 40% bioavailability due to its first pass effect and hence poses problems in development of oral sustained release formulations. Mucoadhesive thermo reversible in situ nasal gel of Amitriptyline HCl was designed and developed to sustain its release due to increased nasal residence time of the formulation. Poloxamer 407 (PF 127) was selected as it has excellent thermo sensitive gelling properties. HPMCK4M was added to impart mucoadhesivity to the formulation and PEG 400 was used to enhance the drug release. Factorial design was employed to assess the effect of concentration of HPMCK4M and PEG 400 on the performance of in situ nasal gel systematically and to optimize the formulation. Optimized in situ nasal gel was evaluated for permeation of drug through nasal mucosa of sheep. Plane polarized microscopic study of optimized formulation indicated transformation of lamellar to cubic crystalline phase which supported permeation kinetics of optimized formulation. Additionally this formulation was proved to be safe as histopathological studies revealed no deleterious effect on nasal mucosa of rat after prolonged exposure of 14 days to optimized formulation. Thus release of Amitriptyline HCl can be sustained if formulated in nasal in situ gel containing PF 127 so as to achieve its prolonged action.