GERD raft

Narrative treatment of GERD: focus on the lower esophageal sphincter (LES) using raft forming in-situ gelling system

Shalinee Jain, Dharmendra Jain


Gastroesophagus reflux disease, acidity and hearts burning are the most common problems, which can be overcome by the raft forming in-situ gel system containing combination of H2 antagonist and GABAB antagonist as well as raft forming agents (alginate, pectin etc.). GERD develops when the reflux of the gastric contents occur into the esophagus which cause various complication into GIT. The main cause of GERD is an abnormal lower esophageal sphincter (LES) pressure and increased reflux during transient LES relaxation. This review mainly focus on the formulation development for reducing the transient lower esophageal sphincter relaxation (TLESR) rate, attenuating esophageal sensitivity and developing esophageal mucosal protectants. For this purpose GABAB  is used which reduces TLESR rate by 40-50% and reflux episodes by 70%, also increase LES pressure and H2 antagonist is used as antisecretory agent in terms of symptomatic relief and mucosal healing. The combined effect of raft forming gelling system is more effective. The review also focuses on the physiological factors, physicochemical factors and formulation factors to be considered in the development of the raft forming system.


GERD; Raft; LES; In-situ gel; GABAB antagonist

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I.S. Sengupta, S.H. Shah, N. Shah, A review on alginate forming in-situ gel for treating peptic ulcers and reflux disorders. J. Pharm. Sci. Bio- Sci. Res. 2015, 5, 172-179.

R.R. Jivania, C.N. Patel, D.M. Patel, N.P. Jivani. Development of a Novel Floating In-situ Gelling System for stomach specific drug delivery of narrow absorption window drug Baclofen. Iran J. Pharm. Res. 2010, 9,359-368.

M.F. Vaezi, J.E. Richter. Role of acid and duodenogastroesophageal reflux ingastroesophageal reflux disease. Gastroenterology, 1996, 111, 1192-1199.

J.K. Patel, J.R. Chavda, M.K. Modasiya. Floating In Situ gel based on Alginate as Carrier for Stomach-Specific Drug Delivery of Famotidine, Int. J. Pharm. Sci. Nanotech. 2010, 3, 1092-1104.

V.D, Prajapati, G.K. Jani, T.A. Khutliwala. Raft forming system— an upcoming approach of gastroretentive drug delivery system, J Control Release. 2013, 92,153-154.

S.J. Spechler, Epidemiology and natural history of gastroesophageal reflux disease. Digestion. 1992, 51, 24–29.

Y.L. Yeong, E.L. Kenneth, Pathophysiology of gastroesophageal reflux disease, Best Pract. Res. Cl. Ga. 2013, 27, 339-351.

S. Pant, A. Badola, P. Kothiyal. A review on gastroretentive drug develops. Pharmacy Life Sci. 2016, 5, 2178-2187.

P.J. Kahrilas, GERD pathogenesis, pathophysiology, and clinical manifestations, Cleve. Clin. J. Med. 2013, 70, S4-S5.

P.O. Katz, L.B. Gerson, M.F. Vela, Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am. J. Gastroenterol. 2013, 108, l308-328.

U. Dutta and P. Moayyedi. Management of reflux-related symptoms. Best Pract. Res. Cl. Ga. 2013, 27, 387-400.

C. Hom and M.V. Vaezi. Extraesophageal manifestations of gastroesophageal reflux disease. Gastroenterol. Clin. North Am.2013, 42, 71-91.

J.P. Galmiche, R.E. Clouse, A. Balint, Functional esophageal disorders, Gastroenterology, 2006, 130, 1459–65.

A. Patrick. Gastroesophagus reflux disease (GERD): A review of conventional and alternative treatments. Altern. Med. Rev. 2011, 16, 116-133.

R.K. Mittal, D.H. Balaban, The esophagogastric junction. N. Engl. J. Med. 1997, 336, 924–932.

J. Liu, V. Parashar, R.K. Mittal. Asymmetry of the lower esophageal sphincter pressure: is it related to the muscle thickness or shape of the lower esophageal sphincter? Am. J. Physiol. 1997, 272, G1509-G1517.

B. Lehmann, J.M. Jensen, Boeckxstaens GE, GABAB receptor agonism as a novel therapeutic modality in the treatment of gastroesophageal reflux disease. Adv. Pharmacol. 2010, 58, 87-31.

K.S. Sree, E. Jeevitha, C.P. Kumar. Gastroesophageal reflux disease: a mini review. Int. J. Recent. Sci. Res. 2015, 6, 5843-5846.

C.S. Winan, Manometric asymmetry of the lower esophageal sphincter pressure zone. Am J Dis. 1977, 22, 348-354.

N.E. Diamant. Pathophysiology of gastroesophageal reflux disease. 2006, doi: 10.1038/gimo21.

P.J. Kahrilas, N.J. Shaheen, M.F. Vaezi. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease, Gastroenterology. 2008, 135, 1392-1413.

Q. Zhang, A. Lehmann, R. Rigda et al. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA (B) agonist Baclofen in patients with gastro oesophageal reflux disease. Gut. 2002, 50, 19–24.

B.Y. Choi, H.J. Park, S.J. Hwang, et al. Preparation of alginate beads for floating drug delivery system: effects of CO2 gas-forming agents, Int. J. Pharm. 2002, 239, 81-91.

N.S. Brahma, H.K. Know. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention, J Control Release. 2000, 63, 235-259.

A.Y. Pawar, K.R. Jadhav, M.N. Nikam. A raft forming System: An novel approach for Gastroretention, Int. J. Pure App. Biosci. 2015, 4, 179-180.

N. Kerdsakundee, S. Mahattanadul, R. Wiwattanapatapee. Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit EPO solid dispersions for gastric ulcer treatment. Eur. J. Pharm. Biophar. 2015, 15, 939-940.

K.G. Mandel, B.P. Daggy, D.A. Brodie, et al. Alginate-raft formulations in the treatment of heartburn and acid reflux. Aliment Pharmacol Ther. 2000, 14, 669-690.

K. Soppimath, T. Aminabhavi, A. Dave, S. Kumbar et al. Stimulus-responsive ―smart hydrogels as novel drug delivery systems. Drug Dev. Ind. Pharm. 2002, 28, 957-974.

P. Tanvi, A. Talele, S. Kumar, A. Jadhav. Formulation, optimization and evaluation of raft forming tablet of nizatidine. Indo. Amer. J. of Pharm. Res. 2015, 5(3), 1177-1190.

N. Vadgama, M. Baladaniya. Gastro retentive insitu gel formulation -an overview. Int. Bulletin Drug Res. 2013, 3, 69-82.

C. Jain, V. Kumar, S. Singh, et al. Newer Trends in In Situ Gelling systems for controlled ocular drug delivery. J. Anal. Pharm. Res. 2016, 2(3), 00022.

A.K. Singh, V. Dubey, V. Arora. Role of natural polymer use in floating drug delivery system. J. Pharm. Sci. Innov. 2012, 3, 11-15.

D. Jain, D. Bar-Shalom. Alginate drug delivery systems: application in context of pharmaceutical and biomedical research. Drug Dev. Ind. Pharm. 2014, 40(12), 1576–1584.

D.P. Shah, G.K. Jani. A newer application of physically modified gellan gum in tablet Formulation using factorial design. ARS Pharmaceutica. 2010, 51(1), 28-40.

M. Patel, R. Patel, V. Patel. Chitosan: A unique pharmaceutical excipient. Drug Deliv. Technol 2008, 5(6), 1-12.

R. Kant, S. Reddy, M.M. Shankraiah, J.S. Venkatesh, et al, In- Situ gelling system- An overview, Pharmacol. Online. 2011, 2, 28-44.

S.J. Sontag, Rolling review: gastro-oesophageal reflux disease, Aliment Pharmacol. Ther. 1993, 7, 293-312.

U. Dutta, D. Armstrong. Novel pharmaceutical approaches to reflux disease. Gastroenterol Clin. North. Am. 2013, 42, 93–117.

B.B. Dean, A.D. Gano, K. Knight, J.J. Ofman, et al. Effectiveness of proton pump inhibitors in nonerosive reflux disease, Clin. Gastroenterol Hepatol. 2004, 2, 656–664.

T. Hershcovici, R. Fass. Pharmacological management of GERD, Trends Pharmacol. Sci. 2011, 32, 258-262.

G.B. Celli and M.L. Brooks. A Ghanem. Development and evaluation of novel alginate based in situ gelling system to modulate the release of anthocyanins, Food Hydrocolloids. 2016, 60, 500-502.

N. Dixit, Floating drug delivery system, J. Curr. Pharm. Res. 2011, 7, 6–20.

P.N. Murthy, A.K. Mahapatra, T.K. Nayak, et al. Formulation, characterization and drug release kinetics of floating drug delivery systems. J. Chem. Pharm. Res. 2015, 7(6), 781-792.

S.H. Shah, J.K. Patel, N.V. Patel. Stomach specific floating drug delivery system: a review. Int. J. Pharm. Tech. Res. 2009, 1, 623-633.

S. Shah, P. Upadhyay, D. Parikh, J. Shah. In Situ Gel: A Novel Approach of Gastroretentive Drug Delivery. Asian. J. Biomed. Pharm. Sci. 2012, 2 (8), 01-08.

A. Jain. New concept: floating drug delivery system. Ind. J. Nov. Drug Deliv. 2011, 3(3), 163-69.

D.V. Patel, A.S. Patel, U.J. Patel, R. J. Patel et al. Recent innovation in gastroretentive drug delivary system. J. Pharmacy Res. 2012, 5(8), 4088-4091.

G. Eccleston, R. Paterson. Gastric raft composition. 2002, US 20020063980.

Y. Ni, M. Y. Kenneth. In situ gelation of pectin substance. 2001, patent 01199941.

I. Singh. Antimicrobials in Higher Plants: classification, mode of action and bioactivities. Chemical Biology Letters, 2017, 4(1), 48-62.

C. Haug, S. Jonat. In situ gelling systems as sustained delivery for front of eye. 2009, US patent 0082221.

A. Jain. New concept: floating drug delivery system. Ind. J. Novel Drug Del. 2011, 3, 163- 69.

J. Dent, H.B. El-Serag, M.A. Wallander et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005, 54, 710–7.

M. Madan et al. In-situ forming polymeric drug delivary system. Indian J. Pharm. Sci. 2009, 71, 242–251.

B.S. Chhikara, S. Kumar, N. Jain, A. Kumar, R. Kumar. Perspectivity of bifunctional chelating agents in chemical, biological and biomedical applications. Chemical Biology Letters, 2014, 1(2), 77-103.

A. Geetha, K. Rajendra C.H.K. Mohan et al. A review on floating drug delivery systems. Int. J. Pharm. Res. Biomed. Analysis 2012, 1, 1-13.

B.N. Singh, K.H. Kim. Floating Drug Delivery Systems: An Approach to Oral Controlled Drug Delivery via Gastric Retention. J. Control Release. 2000, 63, 235–259.

A. Singh, V. Sharma, D. Chauhan. Gastroretentive floating sterculia–alginate beads for use in antiulcer drug delivery. Chem. Eng. Res. Des. 2010, 88, 997-999.

G.M. Rao, P. Murari. Buoyant sustained release drug delivery systems current potentials advancements and role of polymers: a review. Pharmacie Globale. 2012, 2 (01), 1-7.

C. Badoni, A. Ojha, G. Gnanarajan. Review on gastro retentive drug delivery system. Pharma. Innov. 2012, 8, 32–42.

S.H. Shah, J.K. Patel, N.V. Patel. Gastroretentive floating drug delivery systems with potential herbal drugs for Helicobacter pylori eradication: a review. J Chin Integr. Med. 2009, 7(10), 976-982.

P. Kumari, R. Gautam, A. Milhotra. Application of Porphyrin nanomaterials in Photodynamic therapy. Chemical Biology Letters, 2016, 3(2), 32-37.


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