Please cite this article in press as: Hezaveh, H., Muhamad, I.I., Controlled drug release via minimization of burst release in pH-response kappa-carrageenan/polyvinyl alcohol hydrogels. Chem. Eng. Res. Des. (2012), http://dx.doi.org/10.1016/j.cherd.2012.08.014 ARTICLE IN PRESS CHERD-1083; No. of Pages 12 chemical engineering research and design x x x ( 2 0 1 2 ) xxx–xxx Contents lists available at SciVerse ScienceDirect Chemical Engineering Research and Design j ourna l ho me page: www.elsevier.com/locate/cherd Controlled drug release via minimization of burst release in pH-response kappa-carrageenan/polyvinyl alcohol hydrogels Hadi Hezaveh, Ida Idayu Muhamad ∗ Faculty of Chemical Engineering, Universiti Teknologi Malaysia, Johor Bahru, 81310 Johor, Malaysia a b s t r a c t Kappa-carrageenan/polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a natural and non- toxic cross-linker to achieve a controlled drug release. -Carotene was immobilized and the release study was evaluated under in vitro conditions. Monitoring -carotene release was carried out by structure modification using cross-linker and minimization of burst release. It was found that using genipin can stop burst release in the hydrogels and control active material better than native films as a result of structural modification. This suggests that the burst release is depended highly on the degree of cross-linking and the mesh space available for drug diffusion. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are carried out to study the characteristics changes of native and cross-linked hydrogels. Also, field emission scan- ning electron microscope (FESEM) was performed to study microstructure of hydrogels. The transport mechanism seems to be determined by the strength of the gel network due to genipin concentration changes. Finally, diffusion coefficient is determined for native and cross-linked hydrogel. © 2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. Keywords: Hydrogel; Genipin cross-linking; Kappa-carrageenan/polyvinyl alcohol; Burst release; Characterization; Controlled drug release 1. Introduction Hydrogels are polymeric materials with a three-dimensional network structure that are able to swell considerably in aque- ous medium without dissolution (Chen et al., 2004). Since hydrogels are soft tissue biocompatible polymers and able to disperse drugs within the network easily with high degree of controlling on release, extensive efforts has been dedicated to use them in pharmaceutical applications (Vaghani et al., 2011; Risbud et al., 2000). A variety of both natural and synthetic polymeric hydrogels have been used to control the release in drug delivery systems (Kimura, 1993; Mi et al., 2002). Bioactive macromolecules immobilization can improve their protection against degradation at low gastric pH and enzymes, leading to a controlled release of the encapsulated macromolecules (Tan et al., 2010). This encapsulation can be achieved applying natural polysaccharides such as chitosan, alginate and pectin (Leong et al., 2011; Guo and Gao, 2007). ∗ Corresponding author. Tel.: +60 7 5535577; fax: +60 7 5536163. E-mail address: idayu@cheme.utm.my (I.I. Muhamad). Received 13 January 2012; Received in revised form 4 July 2012; Accepted 16 August 2012 Burst release is a nonstady-state and high-rate release of materials that mostly is seen at the beginning of controlled release processes (Huang and Brazel, 2003). The burst release can be caused by numerous reasons such as desorption of the drugs entrapped on the surface of gels (Pekarek et al., 1994), poor distribution of drugs within the hydrogel network dur- ing formation, drying, or storage (Mallapragada et al., 1997; Kishida et al., 1998), heterogeneous nature of polymer network (Patil et al., 1996) or percolation-limited diffusion of entrapped materials (Tzafriri, 2000). In most of cases burst release is considered as a negative phenomenon due to the initial high release rates that may lead to toxicity or tissue irritation in the human body (Huang and Brazel, 2003; Lu and Anseth, 1998; Jeong et al., 2000; Shively et al., 1995). Huang and Brazel (2003) have shown that dry samples can magnified burst effects, but prolonged the release process. Zero order sustained release is often the target of drug delivery and many researchers have taken novel methods to 0263-8762/$ – see front matter © 2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.cherd.2012.08.014