Original Article ANTI-EPILEPTIC DRUG LOADED NIOSOMAL TRANSDERMAL PATCH FOR ENHANCED SKIN PERMEATION SHEFRIN S., SREELAXMI C. S., VISHNU VIJAYAN, SREEJA C. NAIR * Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India Email: sreejacnair@aims.amrita.edu Received: 30 Apr 2018, Revised and Accepted: 09 Jan 2019 ABSTRACT Objective: To formulate and characterize midazolam loaded niosomal transdermal patches for overcoming the frequent dosing and lower bioavailability complications associated with conventional therapy. Methods: The loaded niosomal transdermal patches were prepared by thin film hydration method. The preliminary evaluation and characterization studies was conducted to find the optimised formulation. The in vitro release and ex-vivo permeation studies were investigated. The histopathological studies and stability studies were also assessed. Results: The midazolam loaded niosomal transdermal patches of vesicle size and zeta potential 116.1±84.46 d. nm and 8.56±1.2 mV respectively was formulated. The characterizations of both niosome and niosomal transdermal patches were found to be within the acceptable limits. The in vitro drug release showed an initial burst release followed by sustained release for both optimised niosomal formulation N5 and optimised niosomal transdermal patch formulation NT5with a maximum activity at 97.3±0.35% and 98.9±0.20% respectively. The ex vivo permeation studies of niosomal transdermal patch NT5 was performed which showed a higher permeability than control solution with a flux value of 0.151. The histopathological studies of the optimised formulation showed no detectable lesions upon skin surface and irritations. The stability studies showed that patches were stable over 90 d in different atmospheric conditions. Conclusion: The midazolam loaded niosomal transdermal patch was found to be a promising nano drug delivery alternative which showed better entrapment, release with permeation profile for the daily management of epilepsy with decreased dosing frequency. Keywords: Status epilepticus, Midazolam, Niosome, Soya bean oil, Niosomal transdermal patch, Gelatin © 2019 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2019v11i2.27034 INTRODUCTION Epilepsy is a disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by neurobiologic, cognitive, psychological and social consequences of this condition [1]. The epilepsy associated seizures are distinct to a person and undetectable sometimes and thus require special attention. Seizure is an event of transient occurrence of signs or symptoms due to abnormal, excessive or synchronous neuronal activity of the brain which can vary from short to long periods of vigorous shaking [2]. The excited electrical activity underlying epilepsy is due to biochemical processes at the cellular level promoting neuronal hyperexcitability. Any abnormalities in the normal neuronal transmissions, starting from a single enzyme-receptor abnormality to several key cortical and subcortical structures are involved in generating clinical seizures [3]. Seizures arise from an excessively synchronous excitation and sustained discharge of a group of cortical neurons. Prevailing seizures tend to recrudesce and have no immediate underlying genesis which are the result of excessive and abnormal nerve cell activity in the cortex of the brain [4-6]. Many currently used medications, even intravenous preparations are found to be least effective in early stages of epilepsy treatment [7]. The currently used major formulations for treatment of epilepsy include oral dosages which were once promising approaches for treatment methods but were less efficient in its therapeutic effect [8]. Novel drug delivery research provide a wider opportunity for these limitations [9-11]. Niosomes are nanometre size hydrated vesicles composed of non-ionic lamellar lipid bilayer posing an amphiphilic infrastructure [12-15]. The drug gets encapsulated within the amphiphilic system of the biodegradable and biologically compatible carrier system [16]. The novel carrier molecules are formulated by admixture of non-ionic surfactants like Span 60 or from dialkylpolyglycerol ether class which is stabilised by incorporating waxy steroids like cholesterol [17-20]. The niosomes are already leading in the market where they are used to incorporate various anti-cancer, anti-inflammatory drugs as well as hormonal preparations [21]. Niosomes possess advantages than conventional liposomes and tackles the susceptibility of phospholipids to undergo oxidative degeneration and variations in quality of lipids [22]. The transdermal route of drug administration ensures systemic delivery of drug by applying a drug formulation onto intact and healthy skin thus ensuring sustained drug release and bypass of first-pass metabolism [23-26]. Transdermal drugs significantly delivers molecules in a potent quantity that overcome the conventional problems of oral dosing. Thusthe aim of the study was to develop midazolam loaded niosomal transdermal patchas an effective substitute for the existing maintenance therapiesused for controlling epileptic seizures [27]. MATERIALS AND METHODS Materials and excipients The drug of choice, midazolam, was provided as a gift sample by Lake Chemicals Private Limited, Bangalore. Soya bean oil was obtained, fromSigma Aldrich. All other chemicals used in the experiment were of analytical grade. Preformulation studies Fourier transform infrared (FTIR) spectroscopy The FTIR spectra of drug and excipients were obtained to ascertain the compatibility between midazolam and selected polymers using FTIR spectrophotometer by KBr pellet method [28]. Solubility studies Solubility studies of drug were determined in different solvents such as distilled water, ethanol, methanol, isopropyl alcohol, acetone, n- butyl alcohol and phosphate buffer pH (5.5). Melting point of the drug The melting point of the sample was determined by open capillary method [29]. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 11, Issue 2, 2019