Carbohydrate Polymers 101 (2014) 1234–1242 Contents lists available at ScienceDirect Carbohydrate Polymers j ourna l ho me p age: www.elsevier.com/locate/carbpol Formulation and in vitro evaluation of xanthan gum-based bilayered mucoadhesive buccal patches of zolmitriptan Rewathi R. Shiledar, Amol A. Tagalpallewar, Chandrakant R. Kokare ∗ Department of Pharmaceutics, Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmacy, Narhe, Pune 411041, Maharashtra, India a r t i c l e i n f o Article history: Received 6 August 2013 Received in revised form 14 October 2013 Accepted 21 October 2013 Available online 26 October 2013 Keywords: Zolmitriptan Bilayered Xanthan gum 3 2 factorial design a b s t r a c t A novel bilayered mucoadhesive buccal patch of zolmitriptan was prepared using xanthan gum (XG) as mucoadhesive polymer. Hydroxypropyl methylcellulose E-15 was used as film-former and polyvinyl alcohol (PVA) was incorporated, to increase the tensile strength of the patches. To study the effect of independent variables viz. concentrations of XG and PVA, on various dependent variables like in vitro drug release, ex vivo mucoadhesive strength and swelling index, 3 2 factorial design was employed. In vitro drug release studies of optimized formulation showed initially, rapid drug release; 43.15% within 15 min, followed by sustained release profile over 5 h. Incorporation of 4% dimethyl sulfoxide enhanced drug permeability by 3.29 folds, transported 29.10% of drug after 5 h and showed no buccal mucosal damage after histopathological studies. In conclusion, XG can be used as a potential drug release modifier and mucoadhesive polymer for successful formulation of zolmitriptan buccal patches. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction Buccal mucosa is the most attractive alternative site of sys- temic drug administration amongst the various transmucosal sites available, because it has expanse of relatively immobile smooth muscle and abundant vascularization (Sudhakar, Kuotsu, & Bandyopadhyay, 2006). Buccal cavity provides easy accessibil- ity for self-medication and hence it is well accepted by patients (Abruzzo, Bigucci, Cerchiara, Cruciani, Vitali, & Luppi, 2012; Ratha Adhikari, Nayak, Nayak, & Mohanty, 2010). Moreover it is a poten- tial site for controlled drug delivery of therapeutic agents because of low enzymatic activity compared to the gastro-intestinal tract (Junginger, Hoogstraate, & Coos Verhoef, 1999; Salamat-Miller, Chittchang, & Johnston, 2005). As buccal mucosa is highly per- meable and usually rich in blood supply, it allows rapid uptake of drug in systemic circulation, leading to rapid onset of action (Consuelo, Falson, Guy, & Jacques, 2007) and in most cases avoids degradation by first-pass hepatic metabolism hence leading to high bioavailability (Satheesh Madhav, Shakya, Shakya, & Singh, 2009). Furthermore, buccal mucosa has several advantages like, it shows short recovery times after stress or damage, is tolerant to potential allergens (Scholz, Wolff, Schumacher, & Giannola, 2008; Shojaei, 1998) and provides intimate contact between a dosage form and the absorbing tissue (Bruschi & Freitas, 2005). It has versatility ∗ Corresponding author. Tel.: +91 2066831802/820; fax: +91 2066831816. E-mail addresses: rewathishiledar@gmail.com (R.R. Shiledar), tirupati21@rediffmail.com (A.A. Tagalpallewar), kokare71@rediffmail.com (C.R. Kokare). in designing unidirectional or multidirectional release system for both, local or systemic action (Vasantha, Puratchikody, Mathew, & Balraman, 2011). Various buccal adhesive delivery devices have been developed such as, buccal tablet, buccal films, buccal wafers, buccal gels and ointments (Hearden et al., 2012). But among vari- ous buccal dosage forms, buccal patches provide more flexibility, as they can be very easily administered and removed from the appli- cation site, terminating the input of drug whenever desired (Ratha Adhikari et al., 2010). The patches also have improved patient com- pliance due to their small size and reduced thickness (Morales & Mc Conville, 2011) and obviate the need for water. But one particular problem associated with buccal drug delivery system is the short residence time at the site of application. Use of bioadhesive poly- mers may overcome this problem (Perioli et al., 2004). Bioadhesive polymers are generally classified as natural and synthetic poly- mers (Salamat-Miller et al., 2005). But natural polysaccharides are generally preferred over the synthetic polymers, because they are non-toxic, less expensive and freely available (Bhardwaj, Kanwar, Lal, & Gupta, 2000). In this study xanthan gum (XG), a high molecular weight extra- cellular heteropolysaccharide, produced by fermentation with the Gram-negative bacterium Xanthamonas campestris, (Talukdar & Kinget, 1995) was used for modifying drug release properties and mucoadhesivity. It is a heteropolysaccharide and the primary struc- ture of XG consists of repeated pentasaccharide units formed by two glucose units, two mannose units, and one glucuronic acid unit, in the molar ratio 2.8:2.0:2.0. Its main chain consists of - d-glucose units, which are linked at the 1 and 4 positions. Presence of glucuronic acid in side chains gives this polymer a negative charge. XG is a high molecular weight naturally produced cellulose 0144-8617/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.carbpol.2013.10.072