Gastroretentive Floating-Bioadhesive Drug Delivery System for Rebamipide: Design, In vitro and In vivo Evaluation



  • Ramarao Ajmeera
  • Rajesh Gollapudi


Rebamipide is an amino acid analog of 2-(1H)-quinolinone used in the treatment of peptic ulcer. Here we sought to formulate and evaluate gastroretentive floating-bioadhesive tablets of rebamipide to increase the gastric residence time and further compare their pharmacokinetics with conventional immediate release tablets. Floating-bioadhesive tablets of rebamipide were prepared with combination of Polyox WSR 303 and CP 971P/HPMC K4M and Sodium CMC by direct compression method. The prepared formulations were evaluated for hardness, thickness, weight variation, friability, drug content, in vitro buoyancy and drug release. The optimized formulation (RBF12) floated with a lag time of 28.3 ± 3.2 sec, duration of floating 12 h and released about 99.91 ± 1.84% of drug in 12 h, and then followed non-Fickian diffusion release mechanism with n value of 0.635. The RBF12 tablets with BaSO4 remained in stomach for 5.13 ± 0.64 h (n=3) in radiological studies. The formulation, RBF12 exhibited maximum bioadhesive strength (1.346 ± 0.110 N) than other formulations. The bioavailability studies were carried out for the optimized formulation (RBF12) and compared with that of reference IR tablets “Rebagen” in nine healthy human volunteers. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0–∞, and MRT of RBF12 and IR tablets. The increase in relative bioavailability of RBF12 was 1.7-fold when compared to reference IR tablets. The increased relative oral bioavailability may be due to the floating-bioadhesive mechanism of dosage form, which is desirable for drugs absorbed from the upper part of gastrointestinal tract.


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Floating-bioadhesive, rebamipide, ex vivo bioadhesion, in vivo radiological study, pharmacokinetics




How to Cite

Ajmeera R, Gollapudi R. Gastroretentive Floating-Bioadhesive Drug Delivery System for Rebamipide: Design, In vitro and In vivo Evaluation. Scopus Indexed [Internet]. 2019 May 31 [cited 2024 May 20];12(3):4534-43. Available from:



Research Articles


Banker GS and Anderson NR (1987). Tablets. In: Lachmann L, Liberman HA, Kaing JL, Eds. The theory and practice of industrial pharmacy. 3rd ed. Mumbai: Varghese publishing house, Bombay, p.297-99.
Baumgartner, S., Kristl, J., Vrecer, F., Vodopivec, P., and Zorko, B., (2000). Optimization floating matrix tablets and evaluation of their gastric residence time. Int. J. Pharm. 195: 125-135.
Chen J, Blevins WE, Park H, and Park K (2000). Gastric retention properties of superporous hydrogel composites. J.Control. Release 64(1-3): 39-51.
Chitnis VS, Malshe VS, and Lalla JK (1991). Bioadhesive polymer synthesis, evaluation and application in controlled release tablets. Drug Dev Ind Pharm 17: 879-892.
Chueh HR, Zia H, and Rhodes CT (1995). Optimization of sotalol and bioadhesive extended-release tablet formulations. Drug Dev Ind Pharm 21: 1725-1747.
Doodipala N, Palem RC, Reddy S, and Rao Y (2011). Pharmaceutical development and clinical pharmacokinetic evaluation of gastroretentive floating matrix tablets of levofloxacin. Int J Pharm Sci Nanotech 4: 1463-1469.
El Gamal SS, Naggar VF, and Allam AN (2011). Optimization of acyclovir oral tablets based on gastroretention technology: Factorial design analysis and physicochemical characterization studies. Drug Dev Ind Pharm. 37(7): 855-867.
El-Zahaby SA, Kassem AA, and El-Kamel AH (2014). Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in-capsule system for eradication of Helicobacter pylori. Saudi Pharm J 22: 570-579.
Everhart JE (2000). Recent developments in the epidemiology of Helicobacter pylori. Gastroenterol Clin North Am 29: 559-578.
Higuchi T (1963). Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52: 1145-1149.
Indian Pharmacopoeia (1996). The controller of publications: Delhi, Vol. II, p.734-36.
Kawashima Y, Niwa T, Takeuchi H, Hino T, and Ito Y (1991). Preparation of multipleunit hollow microspheres (microballoons) with acrylic resin containing traniplast and their drug release characteristics (in vitro) and floating behaviour (in vivo). J Control Release 16: 279-289.
Korsmeyer RW, Gurny R, Doelker E, Buri P, and Peppas NA (1983). Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm. 15, 25-35.
Manda P, Angamuthu M, Hiremath SR, Raman V, and Murthy SN (2014). Iontophoretic drug delivery for the treatment of scars. J Pharm Sci 103: 1638-1642.
Manda P, Hargett JK, Vaka SR, Repka MA, and Murthy SN (2011). Delivery of cefotaxime to the brain via intranasal administration. Drug Dev Ind Pharm 37: 1306-1310.
Manda P, Sammeta SM, Repka MA, and Murthy SN (2012). Iontophoresis across the proximal nail fold to target drugs to the nail matrix. J Pharm Sci 101: 2392-2397.
Manglani UR, Khan IJ, Soni K, Loya P and Saraf MN (2006). Development and validation of HPLC-UV method for the estimation of rebamipide in human plasma, Indian J Pharm.Sci. 68(4): 475-478.
Megraud F and Lamouliatte H (1992). Helicobacter pylori and duodenal ulcer. Evidence suggesting causation. Dig Dis Sci 37: 769-772.
Nebiki H, Higuchi K, Arakawa T, Ando K, Uchida T, Ito H, Harihara S, Kuroki T, and Kobayashi K (1998). Effect of rebamipide on Helicobacter pylori infection in patients with peptic ulcer. Dig Dis Sci. 43(9 Suppl): 203S-206S.
Patel A, Modasiya M, Shah D, and Patel V (2009). Development and in vivo floating behavior of verapamil HCl intragastric floating tablets. AAPS Pharm Sci Tech. 10(1): 310-315.
Peterson WL, Fendrick AM, Cave DR, Peura DA, and Garabedian-Ruffalo SM (2000). Helicobacter pylori-related disease: guidelines for testing and treatment. Arch Intern Med 160: 1285-1291.
Ponchel G and Irache J (1998). Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 34: 191-219.
Popescu C, Manda P, Juluri A, Janga KY, and Cidda M (2015). Enhanced Dissolution Efficiency of Zaleplon Solid Dispersions via Modified ß-Cyclodextrin Molecular Inclusion Complexes. J Pharm Pharm Sci. 1: 12-21.
Ritger PL and Peppas NA (1987). A simple equation for description of solute release II.
Shargel L, Pong SW, Yu ABC (2005). Applied biopharmaceutics and pharmacokinetics 5th Ed. New York, Mc Graw Hill, 435-475 & 169-176.
Sunil KJ and Manmohan SJ (2009). Lectin conjugated gastroretentive multiparticulate delivery system of clarithromycin for the effective treatment of Helicobacter pylori. Molecular pharmaceutics 6: 295-304.
Tadros MI (2010). Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: Development, optimization and in vitro–in vivo evaluation in healthy human volunteers. Eur. J. Pharm. Biopharm. 74: 332-339.
Vyas SP and Khar RK (2006). Gastro retentive systems. In: Controlled drug Delivery. Vallabh Prakashan, Delhi, India 197-217.
Wagner JG (1969). Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. J. Pharm. Sci. 58: 1253-1257.
Yamsani VV, Gannu R, Kolli C, Rao ME, and Yamsani MR (2007). Development and in-vitro evaluation of buccoadhesive carvedilol tablets. Acta Pharm. 57(2): 185-197.
Yang Y, Manda P, Pavurala N, Khan MA, and Krishnaiah YS (2015). Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems. J Control Release 210: 58-66.