DEVELOPMENT AND EVALUATION OF MUCOADHESIVE NANOGEL OF NEVIRAPINE FOR VAGINAL APPLICATION Original Article SHEIKH SOFIUR RAHMAN * , ABDUL BAQUEE AHMED * Received: 05 Feb 2019, Revised and Accepted: 28 Mar 2018 Department of Pharmaceutics, Girijananda Chowdhury Institute of Pharmaceutical Science, Hathkhowapara, Azara, Guwahati, Assam 781017 Email: sofiurgips@gmail.com ABSTRACT Objective: The main objective of this study was to develop and evaluate Nevirapine nanoparticle loaded mucoadhesive gel (NVP-Np mucoadhesive gel) for vaginal application for the treatment of HIV infection. Methods: NVP loaded nanoparticles were prepared by salting out method followed by incorporation in different gel bases to produce NVP-Np mucoadhesive gel The prepared gels were evaluated for their physicochemical parameters, rheological characteristics, mucoadhesion, in vitro drug release and ex-vivo permeation of drug across porcine vaginal mucosa. Results: The result of FT-IR and DSC study confirmed the absence of incompatibility of NVP with excipients used in the formulations. The particle size of the prepared NVP-Np was found to be 243.8±3.15 nm, a polydispersity index (PI) of 0.787±0.002 and zeta potential value-17.12 mV, which revealed the stability of nanoparticles. All the formulations showed good homogeneity, spreadability, physical appearance and content uniformity. The pH of the mucoadhesive gel formulations was in the range of 3.70±0.03 to 4.56±0.02, which lies in the normal pH range of the vaginal fluid. The cumulative amounts permeated at 6 h were 832.23±63.45 μg/cm 2 , 592.13±82.55 μg/cm 2 and 941.32±81.10 μg/cm 2 from F1(1% Chitosan), F2(1% Carbopol 974P) and F3 (1% HPMC K100M) respectively. A linear relationship [r 2 Conclusion: In conclusion, NVP-Np mucoadhesive gel was prepared successfully using salting out followed by a homogenization technique for vaginal application of NVP for the prophylaxis of HIV infection. >0.9 (0.97 n 0.99)] was observed between the percentage cumulative amount permeated and time, indicating zero order kinetics. Keywords: Nevirapine, Mucoadhesive gel, HIV infection, Rheological characteristics, Ex-vivo evaluation © 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.2019v11i3.32353 INTRODUCTION Public health, all over the world is facing a serious challenge as occurrences of HIV have become pandemic [1, 2]. A recent report states that 19 million out of 35 million HIV positive people are unaware that they have acquired the virus. Though there are no reports of new HIV infections in the past 10 y, still new methodologies for the prevention of HIV infections is the need of the hour [1]. The HIV pandemic has pushed researchers to explore the development of new preventive technologies. Data collected from the developing countries shows that the occurrence of HIV positive is 4 times higher in the case of women aged up to 24 y compared to a man of the same age group. In 2012, there were reports of 2 million new adult infections, especially young African women. Such fig. are mostly seen in developing countries and highlight the vulnerability of women to HIV infections. However, in most countries the use of condoms, (mostly men condom) is the only method to control HIV infection, women cannot insist to use it. Moreover, women who want to conceive cannot use condoms [3]. As revised, elsewhere rings gels films and creams are typical vaginal dosage forms with advantages for particular drugs and particular indications [4]. The development of nanoparticles based vaginal drug delivery mainly focused on pre-exposure prophylaxis. Nanoparticles can provide sustained release of microbicide drugs, which is necessary for maintaining protective drug concentrations between the time of dosing and the time of intercourse. Drug release from nanoparticles can result in more controlled vaginal absorption compared to a drug depot like a vaginal gel, thereby potentially requiring reduced amounts of the drug. Nanoparticles can be designed to contain multiple modalities, to target specific cells, and to have intrinsic antimicrobial activity [4]. NVP, chemically known as 1-cyclopropyl-5,11-dihydro-4-methyl-6H- dipyrido [3,2-b: 2',3'-e] [1, 4] diazepine-6-one is a non-nucleoside reverse transcriptase inhibitor, active against herpes simplex virus type 1 and 2 and against varicella zoster virus1-2. It is a potent non- nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for the treatment of HIV infection and AIDS. NVP binds directly to reverse transcriptase and blocks the RNA- dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of NVP does not compete with template or nucleoside. The most common adverse effect of NVP is the development of mild or moderate rash (13%) [5]. Mucoadhesive nanogels have gained greater attention as an alternative to conventional gels in the last decade. Mucoadhesive nanogels are easier to handle and administer than conventional gels due to their lesser viscosity in room temperature. On the other hand, the high viscosity of the nanogels at body temperature can minimize chances of gel leakage. Hence developing a mucoadhesive nanogel of NVP may increase the residence time of the formulation and to rapidly penetrate through vaginal mucus in order to deliver the drug to the vaginal epithelium and thereby expected to improve the therapeutic effectiveness of the NVP in the vaginal cavity. Thus, the main objective of this study was to develop and evaluate Nevirapine nanoparticle loaded mucoadhesive gel (NVP-Np mucoadhesive gel) for vaginal application for the treatment of HIV infection. MATERIALS AND METHODS NVP was obtained from Astrix Laboratories Limited (Hyderabad, India) Chitosan was purchased from Sigma–Aldrich (Denmark) Polyvinyl alcohol (PVA), Carbopol 974P, Carboxymethyl cellulose (CMC), HPMC K100M, methylparaben and MgCl 2 were purchased from Sigma–Aldrich (Denmark). All chemicals and solvents used in this study were of analytical Grade. HPLC-grade acetonitrile, methanol, potassium phthalate and ammonium acetate were purchased from Sigma (Denmark). Glacial acetic acid (purity 99.8%) was obtained from Merck (Darmstadt, Germany). Phosphate buffer International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 11, Issue 3, 2019