Original Article SYNTHESIS AND CHARACTERIZATION OF A NOVEL MUCOADHESIVE DERIVATIVE OF PSYLLIUM SEED POLYSACCHARIDE MONICA R. P. RAO *1 , SNEHAL R. GAIKWAD 1 , PRACHI M. SHEVATE 1 1 Department of Pharmaceutics, AISSMS College of Pharmacy, Near RTO, Kennedy Road, Pune 411001, Maharashtra, India Email: monicarp_6@hotmail.com Received: 22 Jul 2016 Revised and Accepted: 09 May 2017 ABSTRACT Objective: In the present study, thiol-functionalization of psyllium seed polysaccharide (PSY) was cross-linked with thioglycolic acid by esterification in an attempt to reveal the mucoadhesive properties of thiolated psyllium seed polysaccharide (TPSY). Methods: The crosslinking was carried out by the microwave-assisted method. A simplex centroid design was employed to systematically study the mucoadhesive strength, mucoadhesive retention time and drug release profile. Comparative evaluation of carbopol-based ciprofloxacin hydrochloride (HCl) tablets containing PSY and TPSY was carried out. Acute oral toxicity studies and repeated oral toxicity for TPSY were also conducted. Results: Thiol-functionalization was confirmed by-SH stretch in Fourier Transform infra-red spectra at 2353 cm -1 . Thiolation was observed in thiolated PSY (TPSY) by a change in the surface morphology of psyllium from fibrous to granular and resulted in 82 %swelling in deionized water. TPSY was found to contain 102.35 mmol of thiol groups/g as determined by the Ellman’s method. The percent increase in mucoadhesive strength of TPSY was found to be 50.31 % as compared to PSY and 128.30 % as compared to carbopol. The percent increase in mucoadhesive retention time of TPSY was found to be 110 % as compared to PSY and 50 % as compared to carbopol. Conclusion: Mucoadhesion strength and mucoadhesive retention time were greater of tablets containing a higher amount of TPSY. Further, the acute oral toxicity studies and repeated oral toxicity for TPSY proved it as non-toxic and hence safe for human use. Keywords: Psyllium seed polysaccharide, Crosslinking, Microwave assisted, Thiolated psyllium seed polysaccharide © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijpps.2017v9i6.14221 INTRODUCTION Natural polysaccharides have widespread applications as biopolymers as they are economical, easily available in a variety of structures. They can be modified easily by the chemical and biochemical process. Along with other properties like stability, safety and biodegradability, they suggest use in targeted drug delivery systems. Also, they find extensive applications in pharmaceutical and food industry because of their diversity in structure and properties [1, 2]. Psyllium, also known as ispaghula comprises of seed husks of Plantago ovata forsk (family Plantaginaceae). The laxative and prolonged action of Plantago husk have been attributed to the gel forming fraction of the husk. Psyllium mucilage obtained from psyllium husk is white fibrous hydrophilic material that forms a clear colourless mucilaginous gel by absorbing water. The polysaccharides extracted from the husk of Plantago ovata have been chemically characterised to contain a high proportion of hemicellulose which is the alkali soluble fraction of the husk. It consists of highly branched acidic arabinoxylan comprising of xylan backbone chain with xylose and arabinose forming the side chains [3]. Psyllium husk has been reported for the treatment of constipation, diarrhea, irritable bowel syndrome, inflammatory bowel disease ulcerative colitis, colon cancer, diabetes and hypercholesterolemia [4]. Phosphorylated PSY has been investigated as a release retardant and binder [5, 6]. Acrylamide-crosslinked psyllium husk is reported as hydrogel for antibiotic drug delivery [7]. Psyllium husk radiated by crosslinked N-vinyl pyrrolidone has been proved as hydrogels for anticancer drug delivery [8]. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome [9]. Mucoadhesion of natural polymers by thiolation has been used to improve the mucoadhesive and cohesive properties of the polymers. Hydroxyethylcellulose (HEC) modified with thiourea was studied for mucoadhesive delivery systems [10]. Chitosan was cross-linked with 2-iminothiolane and reported as having increased mucoadhesive properties [11]. Carboxymethyl dextran was modified by the covalent attachment of cysteine which improved the mucoadhesive properties [12]. In the present study, an attempt was made to improve the mucoadhesive properties of PSY by thiol-functionalization [13]. Thiolation was carried out using the microwave-assisted method to improve the efficiency of the synthetic process [14, 15]. Thiol group estimation was done by Ellman’s reagent assay. The thiolated conjugate (TPSY) was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-Ray diffractometry (XRD) and field emission scanning electron microscopy (FESEM). Mucoadhesive characteristics of psyllium were comparatively evaluated with thiolated-psyllium by conducting tensile tests employing texture analyser. Acute oral toxicity and repeated oral toxicity studies for TPSY were also conducted. A simplex centroid design containing 7 experimental runs to evaluate the effect of polymers i.e. PSY, TPSY and carbopol was employed to determine their effect on three responses i.e. mucoadhesive strength, retention time and percent drug release and their interaction. Ciprofloxacin HCL (CIP) was selected as a model drug for preparing the tablets. MATERIALS AND METHODS Materials Psyllium seeds were obtained from Manakarnika Aushadalay, Pune. Thioglycolic acid was a gift sample from Molychem, Mumbai. All the other chemicals, solvents and reagents used were of analytical grade and were procured locally. Dialysis membrane (HiMedia LA 401) was used for purification of crosslinked conjugate. Ciprofloxacin HCL (CIP) was supplied by Aarti Drugs Ltd. Mumbai. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 9, Issue 6, 2017