Formulation development and in vitro and in vivo evaluation of gastroretentive floating drug delivery system of Lafutidine

Satish H Patil, Gokul S Talele


Lafutidine a newly developed histamine H2‐receptor antagonist was retained in the stomach and assist in improving the oral sustained delivery of drugs in the gastrointestinal tract. A floating drug delivery system (FDDS) was developed
using the gas forming agents, such as sodium bicarbonate, citric acid with hydrochlorides, such as hydroxyl propyl methyl cellulose (HPMCK 4M, HPMCK15M) and novel Carbopol 71G. Polymer with lower viscosity was found to be beneficial
than higher viscosity polymer in improving the release properties of gastroretentive FDDS. The prepared tablets of various formulations were evaluated for a total floating time, buoyancy lag time, and percentage drug released.The formulation code HF3 having HPMCK4M showed better results it may be useful for prolonged drug release in the stomach to improve the
bioavailability and reduced the dose frequency. Non‐Fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer‐Peppas. In vivo study was per formed using the rabbits by X‐ray imaging technique; radiological evidences suggest that, a formulated tablet was well floated more than 10 h in rabbit’s stomach.Optimized floating tablets showed no significant changes in the physical appearance, drug content, total buoyancy time, and also in vitro dissolution pattern after storage at 40°C/75% relative humidity for 3 months.

Full Text:



Ikawa K, Shimatani T, Hayato S, Morikawa N, Tazuma S. Pharmacokinetic

and pharmacodynamic properties of lafutidine after postprandial oral

administration in healthy subjects: Comparison with famotidine. Biol

Pharm Bull 2007;30:1003‐6.

Onodera S, Shibata M, Tanaka M, Inaba N, Yamaura T, Ohnishi H.

Gastroprotective activity of FRG‐8813, a novel histamine H2‐receptor

antagonist, in rats. Jpn J Pharmacol 1995;68:161‐73.

Yamagishi H, Koike T, Ohara S, Horii T, Kikuchi R, Kobayashi S, et al.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H2

receptor antagonist, than by the proton pump inhibitor lansoprazole.

World J Gastroenterol 2008;14:2406‐10.

Onodera S, Shibata M, Tanaka M, Inaba N, Arai Y, Aoyama M, et al.

Gastroprotective mechanism of lafutidine, a novel anti‐ulcer drug with

histamine H2‐receptor antagonistic activity. Arzneimittel for schung


Ichikawa T, Ishihara K, Saigenji K, Hotta K. Lafutidine‐induced

stimulation of mucin biosynthesis mediated by nitric oxide is limited

to the surface mucous cells of rat gastric oxyntic mucosa. Life Sci


Ichikawa T, Ishihara K, Saigenji K, Hotta K. Effects of acid‐inhibitory

antiulcer drugs on mucin biosynthesis in the rat stomach. Eur J

Pharmacol 1994;251:107‐11.

Inaba N, Shibata M, Onodera S, Tanaka M, Suzuki T, Yamaura T, et al.

Studies on histamine H2‐receptor antagonistic property of FRG‐8813,

a novel anti‐ulcer drug. Nihon Yakurigaku Zasshi 1995;105:231‐41.

Kato S, Tanaka A, Kunikata T, Umeda M, Takeuchi K. Protective effect of

lafutidine against indomethacin‐induced intestinal ulceration in rats:

Relation to capsaicin‐sensitive sensory neurons. Digestion 2000;61:39‐46.

Singh BN, Kim KH. Floating drug delivery systems: An approach to

oral controlled drug delivery via gastric retention. J Control Release


Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery

systems: A review. AAPS Pharm Sci Tech 2005;6:E372‐90.

Rosa M, Zia H, Rhodes T. Dosing testing in vitro of a bioadhesive floating

drug delivery system for oral application. Int J Pharm 1994;105:65‐70.

Dorozyn ski P, Jachowicz R, Kulinowski P, Kwiecin ski S, Szybin ski K,

Skórka T, et al. The macromolecular polymers for the preparation of

hydro dynamically balanced systems: Methods of evaluation. Drug Dev

Ind Pharm 2004;30:947‐57.

Atyabi F, Sharma H, Mohammad H, Fell J. In vitro evaluation of a novel gastro retentive formulation based on ion exchange resins. J Control

Release 1996;42:105‐13.

Korsmeyer R, Gurny R, Peppas N. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25‐35.

Whitehead L, Fell JT, Collett JH, Sharma HL, Smith A. Floating dosage

forms: An in vivo study demonstrating prolonged gastric retention.

J Control Release 1998;55:3‐12.

Desai S, Bolton S. A floating controlled‐release drug delivery system:In vitro‐in vivo evaluation. Pharm Res 1993;10:1321‐5.

Gibaldi M, Feldman S. Establishment of sink conditions in dissolution

rate determinations. Theoretical considerations and application to non

disintegrating dosage forms. J Pharm Sci 1967;56:1238‐42.

Higuchi T. Mechanism of sustained‐action medication. Theoretical

analysis of rate of release of solid drugs dispersed in solid matrices.

J Pharm Sci 1963;52:1145‐9.

Hixson AW, Crowell JH. Dependence of reaction velocity upon surface agitation. Ind Eng Chem 1931;23:923‐93.

Peppas NA. Analysis of Fickian and non‐Fickian drug release from

polymers. Pharm Acta Helv 1985;60:110‐1.

Mathews BR. Regulatory aspects of stability testing in Europe. Drug

Dev Ind Pharm 1999;25:831‐56.



  • There are currently no refbacks.