Carbohydrate Polymers 107 (2014) 31–40 Contents lists available at ScienceDirect Carbohydrate Polymers j ourna l ho me page: www.elsevier.com/locate/carbpol Trigonella foenum-graecum L. seed mucilage-gellan mucoadhesive beads for controlled release of metformin HCl Amit Kumar Nayak a , Dilipkumar Pal b,∗ a Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, Odisha, India b Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Koni, Bilaspur 495 009, C.G., India a r t i c l e i n f o Article history: Received 21 November 2013 Received in revised form 28 January 2014 Accepted 5 February 2014 Keywords: Fenugreek seed mucilage Gellan gum Polymer-blend Mucoadhesion Controlled drug release Metformin HCl a b s t r a c t Fenugreek (Trigonella foenum-graecum L.) seed mucilage (FSM)-gellan gum (GG) mucoadhesive beads containing metformin HCl for oral use were developed through ionotropic-gelation technique. Effects of GG to FSM ratio and cross-linker (CaCl 2 ) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10 h (R 10h , %) of ionotropically-gelled FSM-GG mucoadhesive beads con- taining metformin HCl were optimized by 3 2 factorial design. The optimized mucoadhesive beads showed DEE of 92.53 ± 3.85% and R 10h of 55.28 ± 1.58% and mean diameter of 1.62 ± 0.22 mm. The in vitro met- formin HCl release from these ionotropically-gelled FSM-GG beads was prolonged over 10 h and followed zero-order model with super case-II transport mechanism. The optimized mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and signifi- cant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. © 2014 Published by Elsevier Ltd. 1. Introduction Mucilages are naturally occurring, high molecular weight polyuroides consisting of sugars and uronic acid units (Singh, Kumar, Longyan, & Ahuja, 2009). They are normal physiological products formed within the cell/deposited on it in layers (Prajapati, Jani, Moradiya, & Randeria, 2013a). Plant-derived mucilages are important natural polysaccharides with wide range of phar- maceutical applications such as suspending agents, thickeners, emulsifying agents, binders, disintegrants, film-formers, matrix- formers, mucoadhesive agents, etc. (Kulkarni, Gowthmarajan, Rao, & Suresh, 2002; Prajapati, Prajapati, & Acharya, 2006; Edwin, Edwin, Dosi, Raj, & Gupta, 2007; Nayak, Pal, Pany, & Mohanty, 2010; Pal, Nayak, & Kalia, 2010; Saeedi, Morteza-Semnani, Ansoroudi, Fallah, & Amin, 2010; Avachat, Dash, & Shrotriya, 2011; Nerkar & Gattani, 2011; Prajapati et al., 2013a; Nayak, Pal, & Santra, 2013c). Recently, plant-derived mucilages have been used to develop various mucoadhesive beads as potential drug carriers for controlled drug delivery (Nayak, Pal, & Das, 2013a; Nayak, Pal, Pradhan, & Hasnain, 2013b; Nayak et al., 2013c; Nerkar and Gattani, ∗ Corresponding author at: Department of Pharmaceutical Sciences, Guru Ghasi- das Vishwavidyalaya (A Central University), Koni, Bilaspur, 495 009, C.G., India. Tel.: +91 7389263761. E-mail addresses: drdilip2003@yahoo.co.in, drdilip71@gmail.com (D. Pal). 2011). However, most of these mucoadhesive beads were prepared through physical cross-linking by ionotropic-gelation technique (Nayak et al., 2013a,b,c). In these ionotropically-gelled mucoad- hesive beads, plant-derived mucilages were blended with ionic polymers, mainly. Fenugreek (Trigonella foenum-graecum L.) seed mucilage (FSM) is already investigated as suspending agent (Nayak, Das, & Maji, 2012), binder (Sabale, Patel, Paranjape, & Sabale, 2009), mucoadhesive gelling agent (Dutta & Bandyopadhyay, 2005) and disintegrating agent (Kumar, Patil, Patil, Patil, & Paschapur, 2009). It has antidiabetic property, too (Kumar, Shetty, Sambaiah, & Salimath, 2005). In previous reports, our research group has already reported the utility of FSM as mucoadhesive polymer- blends with two anionic polymers, namely sodium alginate and low methoxy pectin in the development of mucoadhesive beads through ionotropic-gelation technique for the use in oral drug delivery (Nayak et al., 2013a,b). However, no report is available in the literature on the development of mucoadhesive beads made of FSM-gellan gum (GG) blends for controlled drug release. GG is an anionic, linear, exopolysaccharide, produced as a fer- mentation product by pure culture of Psedomonus eloda (aerobic, gram negative non-pathogenic bacterium) (Vijan, Kaity, Biswas, Isaac, & Ghosh, 2012). It is composed of the tetrasaccharide, (1 → 4)-l-rhamnose- (1 → 3)-d-glucose--(1 → 4)-d-glucorunic acid--(1 → 4)-d-glucose as a repeating unit in the molar ratio of 2:1:1 (Emeje, Franklin-Ude, & Odoefule, 2010; Jana, Das, Nayak, http://dx.doi.org/10.1016/j.carbpol.2014.02.031 0144-8617/© 2014 Published by Elsevier Ltd.