Design of a novel crosslinked HEC-PAA porous hydrogel composite for dissolution rate and solubility enhancement of efavirenz M. Mabrouk a,b , D.R. Chejara a , J.A.S. Mulla a,c , R.V. Badhe a , Y.E. Choonara a , P. Kumar a , L.C. du Toit a , V. Pillay a, * a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa b Biomaterials Department, National Research Centre, 33El Bohouth St.(former EL Tahrir St.), Dokki, Giza P.O. 12622, Egypt c Department of Pharmaceutics, M.M.U. College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India A R T I C L E I N F O Article history: Received 6 March 2015 Received in revised form 27 May 2015 Accepted 31 May 2015 Available online 3 June 2015 Keywords: Hydrogel composite Physical crosslinking Efavirenz Rheology Dissolution rate Oral solubility A B S T R A C T The purpose of this research was to synthesize, characterize and evaluate a Crosslinked Hydrogel Composite (CHC) as a new carrier for improving the solubility of the anti-HIV drug, efavirenz. The CHC was prepared by physical blending of hydroxyethylcellulose (HEC) with poly(acrylic acid) (PAA) (1:1) in the presence of poly(vinyl alcohol) (PVA) (as a crosslinker) (1:5) under lyophilization. Efavirenz was loaded in situ into the CHC in varying proportions (200–600 mg). The CHC demonstrated impressive rheological properties (dynamic viscosity = 6053 mPa; 500 s 1 ) and tensile strength (2.5 mPa) compared with the native polymers (HEC and PAA). The physicochemical and thermal behavior also confirmed that the CHC was compatible with efavirenz. The incorporation of efavirenz in the CHC increased the surface area (4.4489–8.4948 m 2 /g) and pore volume (469.547–776.916 Å) of the hydrogel system which was confirmed by SEM imagery and BET surface area measurements. The solubility of efavirenz was significantly enhanced (150 times) in a sustained release manner over 24 h as affirmed by the in vitro drug release studies. The hydration medium provided by the CHC network played a pivotal role in improving the efavirenz solubility via increasing hydrogen bonding as proved by the zeta potential measurements (18.0 to +0.10). The CHC may be a promising alternative as an oral formulation for the delivery of efavirenz with enhanced solubility. ã2015 Elsevier B.V. All rights reserved. 1. Introduction HIV/AIDS is the most deadly disease of our time. Globally an estimated 35.3 million people were living with HIV in 2012. There were 2.3 million new HIV infections globally in 2012, showing a 33% decline in the number of new infections from 3.4 million in 2001. At the same time the number of AIDS deaths is also declining with 1.6 million AIDS deaths in 2012, compared to 2.3 million in 2005 (United Nations AIDS Report, 2013). The continual adminis- tration of high and frequent doses of at least two or more antiretroviral (ARV) drugs improves the pharmacotherapy of patients (Andrews and Friedland, 2000). A limited number of ARVs have been approved by the US FDA for the treatment of AIDS especially for paediatric administration (Giaquinto et al., 2008). Among the ARVs, efavirenz is a widely prescribed HIV-1 specific drug which has very poor aqueous solubility (water solubility = 4 mg/mL). This Non-Nucleoside Reverse Transcript Inhibitor (NNRTI) is utilized in the initial stages of pediatric HIV. However, due to its low bioavailability the drug is administrated in doses between 200 and 600 mg per day (Lindenberg et al., 2004; Wintergerst et al., 2008; Sosnik et al., 2009). The side-effects or potential discontinuation of the treatment course is achieved mainly by cumbersome therapeutic monitoring of efavirenz. During the last decade several researchers have reported on the enhancement of efavirenz solubility using various formulation strategies. For example, Kolhe et al. (2014) reported on the improvement of dissolution and bioavailability of efavirenz using a hydrophilic polymer, surfactant and plasticizer. Sunitha and co- workers (2014) explored the synthesis of self-emulsifying drug delivery systems for improving the oral solubility of efavirenz. Lariz et al. (2014) investigated the effect of solid dispersions of efavirenz in PVP-k30 and Deshmukh and Kulakrni (2012) developed a self-micro-emulsifying drug delivery system of efavirenz with improved dissolution rate for oral delivery. In addition, Chaitanya et al. (2014) demonstrated the individual and combined effects of b-cyclodextrin and Lutrol 1 in enhancing the * Corresponding author. Tel.: +27 11 717 2274; fax: +27 11 642 4355/86 553 4733. E-mail address: viness.pillay@wits.ac.za (V. Pillay). http://dx.doi.org/10.1016/j.ijpharm.2015.05.082 0378-5173/ ã 2015 Elsevier B.V. All rights reserved. International Journal of Pharmaceutics 490 (2015) 429–437 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsev ier.com/locate /ijpharm