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
[6–8], 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