aDepartment of Pharmaceutical Technology,Silpakorn University,NakhonPathom 73000,Thailand

bPharmaceutical Biopolymer Group(PBiG),Faculty of Pharmacy,Silpakorn University,NakhonPathom 73000, Thailand

cDepartment of Pharmaceutical Chemistry,Faculty of Pharmacy,Silpakorn University,NakhonPathom 73000, Thailand

Bioadhesiveness of thiolated pectin for buccal delivery of carbenoxolone sodium

Kamonrak Cheewatanakornkoola,b,*,Sathit Niratisaic, Pornsak Sriamornsaka,b

aDepartment of Pharmaceutical Technology,Silpakorn University,NakhonPathom 73000,Thailand

bPharmaceutical Biopolymer Group(PBiG),Faculty of Pharmacy,Silpakorn University,NakhonPathom 73000, Thailand

cDepartment of Pharmaceutical Chemistry,Faculty of Pharmacy,Silpakorn University,NakhonPathom 73000, Thailand

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Thiolated pectin

Carbenoxolone sodium

Buccal disc

Pectin is a biopolymer that has numerous useful purposes in food and beverage industry,cosmetic products and pharmaceutical felds.One of the important properties of pectin is its bioadhesive properties.Native pectin provides fair bioadhesive properties that can be improved by modifcation of pectin structure.The immobilization of thiol groups on polymer can signifcantly improve the bioadhesive properties due to in situ cross-linking between thiol groups of polymer and mucin[1]. Recently,the dosage forms based on thiolated polymers such as microspheres,nanoparticles,gels,lipid formulations and matrix tablets have been developed for intraoral,peroral,ocular and vaginal drug delivery.Carbenoxolone sodium has been used clinically to treat gastric,peptic,esophageal,oral ulceration and infammation.Electrolyte imbalance is a serious side effect of carbenoxolone when used systemically[2].Therefore,the intraoral dosage form,i.e.,buccal discs,was developed for local treatment of aphthous ulcer using thiolated pectin as bioadhesive polymer.

Two different pectins,that is,low methoxy(degree of esterifcation(DE)of 38%)and high methoxy(DE of 70%)pectins were used as starting materials for the synthesis of thiolated pectin.Briefy,the thiolated pectins were synthesized by esterifcation of pectin with thioglycolic acid(TGA)in the absence or presence of hydrochloric acid[3].The reaction was performed by varying mole ratios of TGA to hydroxyl group of pectin.After synthesis,all samples were purifed by dialysis method and then freeze-dried.Thiolated pectins were subjected to analysis by FTIR spectroscopy.Content of sulfhydryl group was determined by Ellman’s reagent assay,using cysteine as a standard.Viscosity of thiolated pectin solution(about 0.6%w/w)was also determined.To prepare buccal discs, thiolated pectin was dissolved in distilled water,mixed with carbenoxolone sodium at a ratio of 1:4,poured to glass plate and dried at 50°C.The dried samples were ground and compressed to discs.The adhesiveness of pectin discs was tested on porcine buccal mucosa using texture analyzer(TA.XT plus,Stable Micro Systems,UK),with 50-N load cell equipped with bioadhesive holder.The contact force and contact time were set at 0.05 N and 60 s,respectively.Two parameters derived from texture analysis,namely maximum detachment force(Fmax)and work of adhesion(Wad),were used as parameters for comparison of bioadhesive performance.The covalent bond between pectin and TGA was produced through hydroxyl group of galacturonic acid of pectin backbone and carboxyl group ofTGA. From the FTIR spectra,when the amount ofTGA increased,the intensity of carbonyl(C=O)of acid at 1650 cm?1decreased but that of carbonyl of ester at 1750 cm?1increased(Fig.1A),suggesting the increase in esterifcation reaction.The content of sulfhydryl group,both in HMP and LMP,also increased when the amount ofTGA was increased.The viscosity results showed a slightly difference between pectin and thiolated pectin.The bioadhesive properties of thiolated pectins on buccal tissue depended on mole ratios ofTGA to hydroxyl group of pectin.Wadof thiolated pectin prepared at mole ratio of 1:7 exhibited highest value(Fig.1B),resulting from the highest content of sulfhydryl group.

Fig.1–(A)FT-IR spectra of LMP pectin and thiolated pectins prepared at different mole ratios of TGA to hydroxyl group of pectin;and(B)work of adhesion of dried pectin discs(HMP and LMP)against porcine buccal tissue(n=4–6).

R E F E R E N C E S

[1]Bernkop-Schnürch A.Thiomers:a new generation of mucoadhesive polymers.Adv Drug Deliv Rev 2005;57:1569–1582.

[2]Bahulkar SS,Munot NM,Surwase SS.Synthesis, characterization of thiolated karaya gum and evaluation of effect of pH on its mucoadhesive and sustained release properties.Carbohydr Polym 2015;130:183–190.

[3]Sharma R,Ahuja M.Thiolated pectin:synthesis, characterization and evaluation as a mucoadhesive polymer. Carbohydr Polym 2011;85:658–663.

*E-mail address:cheewatanakornk_k@su.ac.th.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.095

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).