Research Article Development, Characterization, and Pharmacodynamic Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems Pankajkumar S. Yadav, 1 Ekta Yadav, 1 Amita Verma, 1 and Saima Amin 2 1 Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS), Allahabad 211 007, India 2 Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi 110 062, India Correspondence should be addressed to Pankajkumar S. Yadav; pypharm@gmail.com and Saima Amin; samin@jamiahamdard.ac.in Received 1 July 2014; Revised 27 October 2014; Accepted 28 October 2014; Published 16 December 2014 Academic Editor: Angel Concheiro Copyright © 2014 Pankajkumar S. Yadav et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Te objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo performance. Te research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along with in vitro dissolution and in vivo pharmacodynamic profling. Based on dissolution profle, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5% w/w), Transcutol P (12.7% w/w), and HCT (4.17% w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological efect of HCT by SNEDDS formulation as compared with plain HCT. 1. Introduction Solubility, together with permeability, plays signifcant role in oral bioavailability of a drug [1]. Many conventional drugs present problems related to low solubility in aqueous medium, resulting in a low absorption rate [2, 3]. Several strategies attempted to increase the solubility of poorly water- soluble drugs, that is, micronization [4, 5], solid dispersion [68], complexation [9, 10], and so forth. Lipid based formulation represents a distinctive and relatively novel solution to delivery of poorly soluble com- pounds. A lipid dosage form usually consists of one or more drugs dissolved in a blend of lipophilic excipients such as triglycerides, partial glycerides, surfactants, or cosurfactants [11]. Among the lipid based systems, the self-nanoemulsifying drug delivery system (SNEDDS) is a potential technology to improve the rate and extent of absorption of poorly water- soluble drugs [12]. SNEDDS are isotropic mixtures of drug, lipids, and surfactants, usually with one or more hydrophilic cosolvents or cosurfactants [13]. Hydrophobic drugs can be dissolved in these systems, enabling them to be administered as a unit dosage form for peroral administration. When such a system is released in the lumen of the gastrointestinal tract, it disperses to form a fne oil in water emulsion (micro/nano) with mild agitations provided by gastric mobility. Tis leads to in situ solubilization of drug that can subsequently be absorbed by lymphatic pathways, by passing the hepatic frst- pass efect [14]. Hydrochlorothiazide (HCT) is a potent diuretic drug that is practically insoluble in water and has a solubility of only 250 g/mL in 0.1 N HCl at 25 C[15, 16]. HCT has low toxicity and is widely used in combination with cardiovascular drugs for the treatment of hypertension [17]. Poor water solubility causes possible deviation in the oral bioavailability and, therefore, there is great interest in the development of new drug delivery systems that could enhance the solubility and permeability of HCT and, as a consequence, its bioavail- ability. According to Biopharmaceutical Classifcation System Hindawi Publishing Corporation e Scientific World Journal Volume 2014, Article ID 274823, 10 pages http://dx.doi.org/10.1155/2014/274823