• Laila H. Emara Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • Aya R. Abdou Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • Ahmed A. El-ashmawy Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • Nadia M. Mursi Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt


Objective: The objective of the present study is the preparation of metronidazole (MZ) floating tablets that are designed to retain in the stomach for a long time for better eradication of Helicobacter Pylori (H. pylori), a main cause of peptic ulcer disease.

Methods: Synthetic and natural polymers were studied for their floating potential in the presence of sodium bicarbonate, namely: hydroxypropyl methylcellulose (HPMC), carbopol 974P, sodium alginate{low and medium viscosity (LV & MV) grades}, locust gum and guar gum. Hardness, floating ability, release profiles and kinetics as well as DSC / FT-IR were studied.

Results: Results of both DSC and FT-IR spectroscopy revealed that there was no interaction between the drug and any of the proposed polymers. Carbopol 974P based tablets showed an unacceptable floating lag time (2 h) and did not maintain good tablet integrity. All other formulas were able to float after few seconds and showed buoyancy for more than 24 h. Meanwhile, sustained profiles of MZ release were obtained. After 6 h the amount of MZ released were: 75.11 %, 61.26 %, 54.56 %, 54.25 % and 43.42 % from sodium alginate-LV, HPMC-K4M, guar gum, locust gum and sodium alginate-MV based tablets, respectively. Kinetically, among the 5 assessed models, the release pattern of MZ from the tablets fitted best to Zero order and Hixson & Crowell Cube-Root models.

Conclusion: These stomach targeted dosage forms could maintain the minimum inhibitory concentration for sufficient time to allow for local eradication and thereby achieve better efficiency of therapy with improved patient compliance, reduced costs and minimized side effects caused by immediate release dosage forms.

Keywords: Metronidazole, Floating tablets, HPMC-K4M, Alginates, Gums, Nil, Release kinetics.


Download data is not yet available.


1. Sathish D, Himabindu S, Shravan Kumar Y, Shayeda, Madhusudan Rao Y. Floating Drug Delivery Systems for Prolonging Gastric Residence Time: A Review. Curr Drug Deliv 2011;8(5):494-510.
2. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive Dosage Forms: Overview and Special Case of Helicobacter Pylori. J Cont Rel 2006;111(1-2):1-18.
3. Adibkia K, Hamedeyazdan S, Javadzadeh Y. Drug Release Kinetics and Physicochemical Characteristics of Floating Drug Delivery Systems. Expert Opin Drug Deliv 2011;8(7):891-903.
4. Chawla G, Gupta P, Koradia V, Bansal Ak. Gastroretention a Means to Address Regional Variability in Intestinal Drug Absorption. Pharm Technol 2003;7:52-68.
5. Pawar Vk, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive Dosage Forms: A Review With Special Emphasis on Floating Drug Delivery Systems. Drug Deliv 2011;18(2):97-110.
6. Ali J, Arora S, Ahuja A, Babbar Ak, Sharma Rk, Khar Rk, et al. Formulation and Development of Hydrodynamically Balanced System for Metformin: In Vitro and In Vivo Evaluation. Eur J Pharm Biopharm 2007;67(1):196-201.
7. Baki G, Bajdik J, Pintye-Hodi K. Evaluation of Powder Mixtures and Hydrophilic Gastroretentive Drug Delivery Systems Containing Zinc Acetate and Sodium Bicarbonate. J Pharm Biomed Anal 2011;54(4):711-6.
8. Yao H, Xu L, Han F, Che X, Dong Y, Wei M, et al. A Novel Riboflavin Gastro-Mucoadhesive Delivery System Based on Ion-Exchange Fiber. Int J Pharm 2008;364(1):21-6.
9. Rajinikanth PS, Mishra B. Floating In Situ Gelling System for Stomach Site-Specific Delivery of Clarithromycin to Eradicate H. Pylori. J Cont Rel 2008;125(1):33-41.
10. Gisbert JP, Torrado S, M De La Torre P, Mcnicholl AG, Torrado S. Amoxicillin Gastric Retention Systems for Helicobacter pylori Treatment. Gastroenterology 2011;140(5 Suppl 1):S-880.
11. Jang SW, Lee JW, Park SH, Kim JH, Yoo M, Na DH, et al. Gastroretentive Drug Delivery System of Da-6034, a new flavonoid derivative, for the Treatment of Gastritis. Int J Pharm 2008;356(1-2):88-94.
12. Guan J, Zhou L, Nie S, Yan T, Tang X, Pan W. A Novel Gastric-Resident Osmotic Pump Tablet: In Vitro and In Vivo Evaluation. Int J Pharm 2010;383(1-2):30-6.
13. Jimenez-Martinez I, Quirino-Barreda T, Villafuerte-Robles L. Sustained Delivery of Captopril from Floating Matrix Tablets. Int J Pharm 2008;362(1-2):37-43.
14. Kavimandan NJ, Lakshman JP, Matharu AS, Royce AE, Teelucksingh NR, Ogorka J. Extended Release Gastro-Retentive Oral Drug Delivery System for Valsartan. Ep2061438;2009.
15. Talukder R, Fassihi R. Gastroretentive Delivery Systems: A Mini Review. Drug Dev Ind Pharm 2004;30(10):1019-28.
16. Streubel A, Siepmann J, Bodmeier R. Drug Delivery to the Upper Small Intestine Window Using Gastroretentive Technologies. Curr Opin Pharmacol 2006;6(5):501-8.
17. Murphy CS, Pillay V, Choonara YE, Du Toit LC. Gastroretentive Drug Delivery Systems: Current Developments in Novel System Design and Evaluation. Curr Drug Deliv 2009;6(5):451-60.
18. Singh BN, Kim KH. Floating Drug Delivery Systems: An Approach to Oral Controlled Drug Delivery Via Gastric Retention. J Cont Rel 2000;63(3):235-59.
19. Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating Drug Delivery Systems: A Review. AAPS Pharmscitech 2005;6(3):E372-E90.
20. Pawar Vk, Kansal S, Asthana S, Chourasia Mk. Industrial Perspective of Gastroretentive Drug Delivery Systems: Physicochemical, Biopharmaceutical, Technological and Regulatory Consideration. Expert Opin Drug Deliv 2012;9(5):551-65.
21. Khan GM, Jiabi Z. Formulation and In Vitro Evaluation of Ibuprofen-Carbopol® 974PNF Controlled Release Matrix Tablets III: Influence of Co-Excipients on Release Rate of the Drug. J Cont Rel 1998;54:185-90.
22. Gutiérrez‐Sánchez PE, Hernández‐León A, Villafuerte‐Robles L. Effect of Sodium Bicarbonate on the Properties of Metronidazole Floating Matrix Tablets. Drug Dev Ind Pharm 2008;34(2):171–80.
23. Cedillo‐Ramírez E, Villafuerte‐Robles L, Hernández‐León A. Effect of Added Pharmatose DCL11 on the Sustained‐Release of Metronidazole from Methocel K4M and Carbopol 971P NF Floating Matrices. Drug Dev Ind Pharm 2006;32(8):955-65.
24. Lara-Hernández B, Hernández-León A, Villafuerte-Robles L. Effect of Stearic Acid on the Properties of Metronidazole/Methocel K4M Floating Matrices. Brazilian J Pharm Sci 2009;45:497-505.
25. Asnaashari S, Khoei NS, Zarrintan MH, Adibkia K, Javadzadeh Y. Preparation and Evaluation of Novel Metronidazole Sustained Release and Floating Matrix Tablets. Pharm Dev Technol 2011;16(4):400-7.
26. Murthy RSR. Biodegradable Polymers, Controlled and Novel Drug Delivery. 1st ed. New Delhi: CBS Publishers; 1997. p. 27-51.
27. Bechgaard H, Ladefoged K. Distribution of Pellets in the Gastrointestinal Tract. The Influence on Transit Time Exerted by the Density or Diameter of Pellets. J Pharm Pharmacol 1978;30:690-2.
28. Javadzadeh Y, Hamedeyazdan S, Adibkia K, Kiafar F, Zarrintan MH, Barzegar‐Jalali M. Evaluation of Drug Release Kinetics and Physico‐Chemical Characteristics of Metronidazole Floating Beads Based on Calcium Silicate and Gas‐Forming Agents. Pharm Dev Technol 2009;15(4):329-38.
29. Eftaiha AF, Qinna N, Rashid IS, Al Remawi MM, Al Shami MR, Arafat TA, et al. Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum. Mar Drugs 2010;8:1716-30.
30. Jagdale SC, Patil S, Kuchekar BS. Application of Design of Experiment for Floating Drug Delivery of Tapentadol Hydrochloride. Computational and Mathematical Methods in Medicine 2013:1-7.
31. Abdelbary A, El-Gazayerly ON, Nashwa A. El-Gendy NA, Ali AA. Floating Tablet of Trimetazidine Dihydrochloride: An Approach for Extended Release with Zero-Order Kinetics. AAPS Pharmscitech 2010;11(3):1058-67.
32. Garg R, Das Gupta G. Preparation and Evaluation of Gastroretentive Floating Tablets of Silymarin. Chem Pharm Bull 2009;57(6):545-9.
33. Jain GK. Gums and Mucilages: Versatile Excipients for Pharmaceutical Formulations Drug Delivery Systems. Asian J of Pharm Sci 2009;4:309-23.
34. Ganesh K, Archana D, Preeti K. Natural Polymers in the Development of Floating Drug Delivery Systems: A Review. J of Pharm and Life Sci 2013;2(4):165-78.
35. Marshall BJ. Unidentified Curved Bacilli in Gastric Epithelium in Active Chronic Gastritis. Lancet 1983;1:1273-5.
36. Marshall BJ, Warren JR. Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration. Lancet 1984;1:1311-5.
37. Vakil N, Cutler A. Ten-Day Triple Therapy with Ranitidine, Bismuthcitrate, Amoxicillin and Clarithromycin in Eradicating Helicobacter Pylori. Am J Gastroenterol 1999;94:1197–9.
38. Narkar M, Sher P, Pawar A. Stomach-Specific Controlled Release Gellan Beads of Acid-Soluble Drug Prepared by Ionotropic Gelation Method. AAPS Pharmscitech 2010;11(1):267-77.
39. Shah S, Qaqish R, Patel V, Amiji M. Evaluation of the Factors Influencing Stomach‐Specific Delivery of Antibacterial Agents for Helicobacter pylori Infection. J Pharm Pharmacol 1999;51:667–72.
40. Emara LH, Abdou AR, El-Ashmawy AA, Badr RM, Mursi NM. In Vitro Evaluation of Floating Matrix Tablets of Amoxicillin and Metronidazole for the Eradication of Helicobacter pylori. Int J Pharm Pharm Sci 2012;4(3):671-81.
41. Amiji MM. Tetracycline-Containing Chitosan Microspheres for Local Treatment of Helicobacter pylori Infection. Cellulose 2007;14:3-14.
42. Umamaheshwari RB, Suman R, Jain Nk. Anti-Helicobacter pylori Effect of Mucoadhesive Nanoparticle Bearing Amoxicillin in Experimental Gerbils. AAPS Pharmscitech 2004;5:60-8.
43. Sung JJ, Chung SC, Ling Tk. Antibacterial Treatment of Gastric Ulcers Associated with Helicobacter pylori. N Engl J Med 1995;332 (3):139-42.
44. Dollery C. Therapeutic Drugs. 2nd Ed. Vol. 2, Edinburgh: Churchill Livingstone; 1999.
45. Yang L, Eshraghi J, Fassihi R. A New Intragastric Delivery System for the Treatment of Helicobacter pylori Associated Gastric Ulcer: In Vitro Evaluation. J Cont Rel 1999;57(3):215–22.
46. Sriamornsak P, Asavapichayont P, Nunthanid J, Luangtana‐Anan M, Limmatvapirat S, Piriyaprasarth S. Wax‐Incorporated Emulsion Gel Beads of Calcium Pectinate for Intragastric Floating Drug Delivery. AAPS Pharmscitech 2008;9(2):571-6.
47. Sriamornsak P, Sungthongjeen S, Puttipipatkhachorn S. Use of Pectin as a Carrier for Intragastric Floating Drug Delivery: Carbonate Salt Contained Beads. Carbohydr Polym 2007;67(3):436-45.
48. Ishak Ra, Awad Ga, Mortada Nd, Nour Sa. Preparation, In Vitro and In Vivo Evaluation Of Stomach‐Specific Metronidazole Loaded Alginate Beads As Local Anti‐Helicobacter Pylori Therapy. J Cont Rel 2007;119(2):207–14.
49. Murata Y, Sasaki N, Miyamoto E, Kawashima S. Use of Floating Alginate Gel Beads for Stomach‐Specific Drug Delivery. Eur J Pharm Biopharm 2000;50(2):221–6.
50. Jeong B, Kim SW, Bae YH. Thermosensitive Sol‐Gel Reversible Hydrogels. Adv Drug Deliv Rev 2002;54:37-51.
51. Nama M, Gonugunta CS, Reddy Veerareddy P. Formulation and Evaluation of Gastroretentive Dosage Forms of Clarithromycin. AAPS Pharmscitech 2008;9(1):231-7.
52. United States Pharmacopeia and National Formulary USP 30-NF 25;The United States Pharmacopeial Convention, Inc. :Rockville, MD; 2007. p. 2655.
53. Jiménez‐Castellanos MR, Zia H, Rhodes CT. Design and Testing In Vitro of a Bioadhesive and Floating Drug Delivery System for Oral Application. Int J Pharm 1994;105(1):65-70.
54. Tadros MI. 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 2010;74:332-9.
55. Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Tech 1996;20:64-74.
56. United States Food and Drug Administration. Guidance for industry, dissolution testing of immediate release solid oral dosage forms; 1997.
57. Sood A, Panchagnula R. Drug Release Evaluation of Diltiazem CR Preparations. Int J Pharm 1998;175(1):95–107.
58. Wright MR. The Kinetic Analysis of Experimental Data: An Introduction to Chemical Kinetics. The Atrium, Southern Gate, Chichester, West Suessex P019 8SQ, England: Wiley J and Sons Ltd; 2004. p. 43-95.
59. Philip Ak, Pathak K. Osmotic Flow Through Asymmetric Membrane: A Means for Controlled Delivery of Drugs with Varying Solubility. AAPS Pharmscitech 2006;7(3):E1–E11.
60. Karasulu E, Yesim Karasulu H, Ertan G, Kirilmaz L, Guneri T. Extended Release Lipophilic Indomethacin Microspheres: Formulation Factors and Mathematical Equations Fitted Drug Release Rates. Eur J Pharm Sci 2003;19(2-3):99-104.
61. Ostle B. Statistics in Research: The Iowa State University Press, Ames, Iowa, USA; 1960. p. 64.
62. Parab PV, Oh CK, Ritschel WA. Sustained Release from Precirol® (Glycerol Palmito‐Stearate) Matrix. Effect of Mannitol and Hydroxypropyl Methylcellulose on the Release of Theophylline. Drug Dev Ind Pharm 1986;12(8):1309-27.
63. British Pharmacopoeia. London: The Pharmaceutical Press; 1998. p. 242.
64. United States Pharmacopeia and National Formulary USP 27– NF 22;The United States Pharmacopeial Convention, Inc. :Rockville, MD; 2004. p. 454–8.
65. Singh BM, Kim KH. Floating Drug Delivery Systems: An Approach to Oral Controlled Drug Delivery via Gastric Retention. J Cont Rel 2000;63:235-59.
66. Chavanpatil M, Jain P, Chaudhari S, Shear R, Vavia P. Development of Sustained Release Gastroretentive Drug Delivery System for Ofloxacin: In Vitro and In Vivo Evaluation. Int J Pharm 2005;304:178-84.
67. El Gamal SS, Naggar VE, Allam AN. Optimization of Acyclovir Oral Tablets Based on Gastroretention Technology: Factorial Design Analysis and Physicochemical Characterization Studies. Drug Dev Ind Pharm 2011;37(7):855-67.
68. Steingoetter A, Weishaupt D, Kunz P, Mader K, Lengsfeld H, Thumshirn M, et al. Magnetic Resonance Imaging for the In Vivo Evaluation of Gastric-Retentive Tablets. Pharm Res 2003;20(12):2001-7.
69. Li S, Lin S, Daggy BP, Mirchandani HL, Chien YW. Effect of HPMC and Carbopol on the Release and Floating Properties of Gastric Floating Drug Delivery System Using Factorial Design. Int J Pharm 2003;253:13–22.
70. Devraj, Bhatt DC. Studies on Enteric Coated Sustained Timed-Release Tablets of Metronidazole. J Chem Pharm Res 2010;2(2):226-32.
71. Choudhury PK, Murthy PN, Tripathy NK, Panigrahi R, Behera S. Investigation of Drug Polymer Compatibility: Formulation and Characterization of Metronidazole Microspheres for Colonic Delivery. Webmed Central Pharm Sci 2012;3(3):WMC003128.
72. Purushothaman M, Vijaya Ratna J. Formulation Optimization and Release Kinetics of Metronidazole Matrix, Compression and Spray Coated Tablets: Effect of Organic Acid on Colon Targeted Drug Delivery System. Int J Res Pharm Sci 2010;1(4):551-62.
1590 Views | 4380 Downloads
How to Cite
Emara, L. H., A. R. Abdou, A. A. El-ashmawy, and N. M. Mursi. “PREPARATION AND EVALUATION OF METRONIDAZOLE SUSTAINED RELEASE FLOATING TABLETS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 9, Sept. 2014, pp. 198-04,
Original Article(s)