FORMULATION AND EVALUATION OF ION-SENSITIVE IN-SITU NASAL GEL OF ZOLMITRIPTAN Original Article P. R. PATIL*, V. K. SALVE, R. U. THORAT, S. R. SHAHI Government college of Pharmacy, Department of Pharmaceutics, Hotel Vedant Road, Osmanpura, Aurangabad, Maharashtra, India 431005 Email: chitru.p@gmail.com Received: 10 Jul 2014 Revised and Accepted: 08 Sep 2014 ABSTRACT In situ gel system is novel drug delivery system in which there is transition of sol to gel on external stimuli like change in pH, temperature or change in ion concentration (sol-gel transition). In the present study various formulations were prepared by using gellan gum as gelling agent and HPMC K100 as controlled or sustained release polymer. All the formulations were evaluated for various parameters like pH, viscosity, drug content, gel strength, mucoadhesive strength and drug release. At minimum concentration of polymer lose their integrity and at maximum concentration stiff gel were formed. At optimized concentration of gelling agent and HPMC K100 showed in situ gelling with all parameter in range. In Vitro release data revealed that the optimized formulation showed controlled and sustained drug release pattern. The optimized formulation also obeyed korsmer Peppas model equation and which showed the release exponent n value 0.765. Thus the ex vivo higher bioavailability can be expected from the optimized formulation. Keywords: In situ gelling, Nasal delivery, Migraine, Polymers, Sustained release, Higher bioavailability etc. INTRODUCTION Migraine headache is one of the most common human ailment and the most common complaints of patients evaluated by neurologist. It is a specific neurological syndrome that has a wide variety of manifestations. In recent years, the Nasal route has received a great deal of attention as a convenient and reliable method for the systemic administration of drugs. The nasal cavity as a site for the systemic absorption of drugs has some advantages which include relative large surface area, porous endothelial basement, highly vascularised epithelial layer, high total blood flow/cm 3 This is likely due to extensive presystemic clearance on first pass. As migraine sufferers have markedly reduced functional ability, they would be benefited from acute treatment that helps them to resume their functional activities as quickly as possible. In situ gel, or in vivo gel, environment sensitive gel, is a new dosage form which has been applied as nasal drug delivery recently. Compared with liquid nasal formulations, nasal in situ gels are instilled as low viscosity solutions into the nasal cavity and upon contact with the nasal mucosa, or nasal composition the polymer changes conformation producing a gel, so it cannot only prolong the contact time between the drug and the absorptive sites in the nasal cavity, but also release drug slowly and continuously. Hence, it is especially very useful for those drugs used chronically. The phase transition can be induced by the presence of cations as for gellan gum a shift in pH as for cellulose acetate phthalate, a shift in temperature as for the thermo gelling Poloxamer 407. , avoiding the first pass metabolism and easy access. Zolmitriptan, 4S-4-({3-[2- (dimethylamino) ethyl]-1H-indol-5-yl} methyl)-1, 3-oxazolidin -2- one, is a second –generation triptan prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. It is an effective agent in the treatment of acute migraine attack with or without aura. However, oral bioavailability is poor with only 40 % of the dose reaching systemic circulation. MATERIALS AND METHODS Zolmitriptan was obtained as a gift sample from Emcure Pharmaceuticals pune India HPMC K100 From Colorcon Goa, Gellan Gum(kelcogel) From Signet Pharma, Benzalkonium chloride from Merck Pharma. All the ingredient used were of LR Grade. Preparation of standard curve of Zolmitriptan Accurately weighed 10 mg of Zolmitriptan was dissolved in 100 ml of distilled water to get stock solution of 100μg/ml. From this stock solution aliquots of 0.1, 0.2, 0.3, 0.4, 0.5 ml were withdrawn and further diluted to 10 ml with distilled water to obtain a concentrations range of 1 to 5 μl/ml. The absorbance of the solutions was measured at 283.5 nm by using UV-Vis spectrophotometer. A graph of concentration vs. Absorbance was plotted. (Table 1) Table 1: Absorbance of Standard solutions at 283.5 nm S. No. Conc.(μg/ml) Absorbance 1 10 0.202 2 20 0.367 3 30 0.567 4 40 0.756 5 50 0.933 Fig. 1: Calibration curve of Zolmitriptan Preparation of nasal formulations Gellan gum solutions of various concentrations were prepared by adding the gum to deionised water and heating up to 90°C continuing stirring remi- stirrer. After cooling to below 40°C, HPMC K100, Zolmitriptan (25% w/v), mannitol (5%, w/v), and Benzalkonium chloride (0.01%, w/v) were added and mixed well. Three various kinds of Zolmitriptan in situ gels were prepared at the concentrations of Gellan gum which were 0.3%, 0.6%, 0.9% and with combination of HPMC K100 concentrations0.10%, 0.13% and 0.0.15% (w/v) respectively.(table 2) International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 2, 2015 Innovare Academic Sciences