Delivered by Publishing Technology to: York University Libraries IP: 68.165.121.206 On: Sat, 19 Dec 2015 07:08:15 Copyright: American Scientific Publishers Copyright © 2014 American Scientific Publishers All rights reserved Printed in the United States of America Journal of Bionanoscience Vol. 8, 81–89, 2014 Formulation and Evaluation of Venlafaxine Nanostructured Lipid Carriers Sandeep M. Dange 1 , Meghana S. Kamble 1 ∗ , Kishor K. Bhalerao 2 , Pravin D. Chaudhari 1 , Ashok V. Bhosale 3 , Basavaraj K. Nanjwade 4 , and Saurabh A. Shinde 1 1 Department of Pharmaceutics, P. E. Society’s Modern College of Pharmacy, Nigdi, Pune 411044, Maharashtra, India 2 Department of Quality Assurance, P. E. Society’s Modern College of Pharmacy, Nigdi, Pune 411044, Maharashtra, India 3 Department of Pharmaceutics, P. D. E. A.’s S. G. R. S. College of Pharmacy, Saswad, Pune 411044, Maharashtra, India 4 Faculty of Pharmacy, Department of Pharmaceutics, Omer Al-Mukhtar University, P.O. Box 919, Al-Bayda, Libya Venlafaxine is newer class of antidepressant used in treatment of depression. In the presents study, we aimed to prepare a nanostructured lipid carrier (NLC) gel, for the intranasal drug delivery of Venlafaxine. The Venlafaxine loaded NLCs were prepared by emulsion solvent diffusion and evapo- ration method followed by ultrasonication. Properties of nanostructured lipid carriers such as particle size and its distribution, % Drug loading were investigated. The NLC dispersion was suitably gelled and characterized for drug content, pH, viscosity, in-vitro and ex-vivo release and in-vivo phar- macodynamic study. FTIR and DSC analyses showed no significant chemical interaction between Venlafaxine and excipients in the formulation. The particle size of optimized batch of NLCs was found to be 151.83 nm and zeta potential was found to be - 8.08 mV. Drug loading was found to be 3433 ± 2180%. A toxicological study carried out on sheep nasal mucosa showed no evidence of toxicity of the NLC based gel. The NLC based gel showed a rapid onset alongwith a prolonged duration of action as compared with pure drug solution and NLC dispersion. Keywords: Venlafaxine, Antidepressant, Intranasal, Nanostructured Lipid Carriers. 1. INTRODUCTION Nasal route of administration is a useful delivery route for drugs that are active in low doses, show no or minimal oral bioavailability and when a rapid onset of action of action is desired. The nasal route circumvents hepatic first pass elimination associated with oral delivery and is also easily accessible and suitable for self-medication. 1 2 Ideal candidates in which nasal route can be utilized are the compounds which are generally injected, hardly absorbed after oral administration, unstable in the gastrointestinal tract (GIT), who have poor absorption properties and show rapid and extensive biotransformation. 3 The richly sup- plied vascular nature of the nasal mucosa coupled with its high drug permeation makes the nasal route of adminis- tration attractive for such drugs. 4 Nose to brain delivery is possible by the olfactory region located at the roof of nasal cavity as its neuro-epithelium is the only part of the CNS that is directly exposed to the external environment. From this neuro-epithelium drugs are carried to CNS by the trigeminal nerve systems by a number of mechanisms. 5 Nanostructured lipid carriers (NLCs) are considered to be a promising strategy for drug delivery without any ∗ Author to whom correspondence should be addressed. modification to the drug molecule. Also they are highly lipophilic and this attribute can be utilized to increase per- meability of drug across nasal mucosa. The main objective of the NLC dosage form is to deliver drug by nasal route to brain with maximum drug absorption and minimum side effects. 6 Depression is the most common major mental illnesses associated with a high mortality rate. About 121 million people worldwide are affected by depression. Symptoms of the depression are commonly observed in the age cat- egory of 15–44 years for both the sexes. 7 Venlafaxine is a dual acting antidepressant, and belongs to class of anti-depressants known as serotonin and nor-epinephrine reuptake inhibitors (SNRI). Venlafaxine is amongst the first-line drugs used in the treatment of depression. Ven- lafaxine Hydrochloride (VLF) is a newer drug developed for the treatment of depression and is rapidly absorbed from the GIT, but has extensive hepatic metabolism. Ven- lafaxine Hydrochloride thus has very low oral bioavail- ability of about 40%. This added to other drawbacks of Venlafaxine hydrochloride therapy such as slow onset of action, side effects like tachycardia, increased blood pres- sure, fatigue, headache, dizziness, sexual dysfunction, dry J. Bionanosci. 2014, Vol. 8, No. 2 1557-7910/2014/8/081/009 doi:10.1166/jbns.2014.1209 81