Title: Alginate-sterculia gum gel-coated oil-entrapped alginate beads for gastroretentive risperidone delivery
Author: Hriday Bera Saisharan Goud Kandukuri Amit Kumar
Nayak Shashank Boddupalli
Reference: CARP 9499
To appear in:
Received date: 8-11-2014
Revised date: 6-12-2014
Accepted date: 12-12-2014
Please cite this article as: Bera, H., Kandukuri, S. G., Nayak, A. K., and Boddupalli, S.,Alginate-sterculia gum gel-coated oil-entrapped alginate beads for gastroretentive risperidone delivery, Carbohydrate Polymers (2014), http://dx.doi.org/10.1016/j.carbpol.2014.12.009
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Ac ce pte d M an us cri pt 1
Alginate-sterculia gum gel-coated oil-entrapped alginate beads for gastroretentive risperidone delivery
Hriday Beraa,*, Saisharan Goud Kandukuria,
Amit Kumar Nayakb,* and Shashank Boddupallia a Department of Industrial Pharmacy, Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad, India-500090. b Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj, Odisha, India- 757086. *Corresponding author. E–mail: email@example.com, Phone: +91 8977726256 (H. Bera).
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E–mail: firstname.lastname@example.org, Phone: +91 9583131603 (A.K. Nayak).
Novel floating-mucoadhesive oil-entrapped alginate beads coated with crossslinked alginate-sterculia gum gel membrane was developed for gastroretentive risperidone delivery. Oil-entrapped alginate beads containing risperidone as core were prepared by ionotropic gelation technique.
Effects of polymer to drug ratio and oil to water ratio on drug entrapment efficiency (%) and cumulative drug release after 8 h (%) were studied to optimize the core beads by a 32 factorial design. The optimized beads (F-O) demonstrated drug entrapment efficiency of 83.73 ± 0.81% and cumulative drug release of 70.84 ± 0.27 % after 8 h. The biopolymeric-coated optimized beads exhibited excellent buoyancy, better ex vivo mucoadhesion and slower drug release rate. The drug release profiles of risperidone-loaded uncoated and coated beads were best fitted in
Korsmeyer-Peppas model with Fickian diffusion mechanism. The beads were also examined for the drug-excipients compatibility, drug crystallinity and surface morphology by FTIR, P-XRD and SEM analyses, respectively.
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Keywords: Alginate; Sterculia gum; Olive oil; Floatation; Mucoadhesion; Risperidone. 1. Introduction
Risperidone is an atypical anti-psychotic drug of benzisoxazole class, which is clinically recommended for bipolar disorder and schizophrenia management (Muthu and Singh, 2009). The variable half-life of it (3-20 h) has raised the interest in developing extended-release formulations of risperidone (Badshah et al., 2011). It exhibits an increased solubility at acidic pH relative to the solubility at alkaline pH (Prieto et al., 2011). Therefore, a better drug dissolution and improved oral bioavailability can be ensured through prolonging the gastric residence of risperidone. Numerous oral sustained release gastroretentive drug delivery systems viz., floating systems (Nayak et al., 2013; Malakar et al., 2014), mucoadhesive systems (Pal and Nayak, 2012), expandable or swellable systems (Klausner et al., 2003), high density systems (Rouge et al., 1998), etc. have been developed. Recently, the combined floatation-mucoadhesion approaches for gastroretentive drug delivery have gained importance as these systems display an improved gastroretention by virtue of their floatation and bio-adhesion properties (Rathi et al., 2012;
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Malakar and Nayak, 2013). Currently, various natural polysaccharides are used in the development of gastroretentive drug delivery systems (Malakar et al., 2012; Nayak et al., 2013; Guru et al., 2013).
Sodium alginate, a biodegradable, biocompatible, anionic natural heteropolysaccharide, able to form hydrogel beads by Ca2+ etc., due to intermolecular ionotropic interactions between carboxylic acid groups of alginate molecules and calcium ions (Goh et al., 2012). Calcium alginate beads have been intensively exploited as drug carriers in gastroretentive floating systems (Bera et al., 2009; Malakar et al., 2012).
Unfortunately, alginate floating beads are suffered from low drug entrapment, less floating duration, long floating lag time and burst drug release, which can be improved by the incorporation of additives like low-density oils, effervescent agents, etc. Currently, oil-entrapped alginate floating beads have been established as promising multiple-unit vehicles for gastroretentive drug delivery due to their simplicity in preparation along with easy surface modification (Bera et al., 2009; Malakar and Nayak, 2012). Additionally, low-density oils improve the buoyancy and impose a hydrophobic barrier towards drug escaping from the matrices, which results in higher drug entrapment with prolonged drug release behavior (Malakar and Nayak, 2012).
Recently, a flurry of scientific investigations has employed mucoadhesive biopolymeric coating on gastroretentive floatable systems (Sahasathian et al., 2010; Fahmy, 2012). Moreover, the usage of natural polysaccharides blends is a current trend to improve desired functional properties like drug encapsulation, swelling, drug release and stability (Ahuja et al., 2010). Sterculia gum is a water-soluble polysaccharide obtained from the stem exudates of Sterculia urens (Singh et al., 2010). It is composed of partially acetylated polysaccharides of the substituted rhamnogalacturonoglycan, with residues of D-glucuronic acid, D-galacturonic acid, D-galactose and L-rhamnose (Singh and Sharma, 2008,