Helicobacter pylorus (H. pylori) is a gram-negative, motile, microaerophilic spiral bacterium. Helicobacter species is the causative organism for peptic ulcer. Gastric (mainly peptic) ulcer is one of the major ailments affecting about 60% of human adults and nearly 80% of child population, all H. pylori species cause some degree of persistent inflammation.1) Treatment of H. pylori remain a challenge although H. pylori is highly sensitive to most antibiotics, eradication of H. pylori from patient is difficult, even with the current best therapies.2,3) Conventional tablets and capsules are used for eradication therapy; do not remain in stomach for a long time.4) The various floating preparations such as micro balloons, granules, powders, capsules, tablets, and laminated films has been attempted. 5) An excellent concept of floating system suffers from a disadvantage that it is effective only when the fluid level in stomach is sufficiently high; however, as the stomach empties and the tablet is at the pylorus, the buoyancy of the dosage form may be impeded.6) This serious limitation can be overcome by the use of bio-adhesive polymers to enable it to adhere to the mucous lining of stomach wall. Floating and bio-adhesive drug delivery systems offer the advantages of increased contact time with stomach mucosa, more effective absorption and bioavailability of drugs with absorption windows near proximal intestine and stomach, and low dosing frequencies. 7) In this article a synergism between bio-adhesion and floating property has been explored. Therefore, it is difficult to reach minimum inhibitory concentration in the gastric mucosa where H. pylori colonizes. To overcome these problems, a new concept is proposed based on a floating and bio-adhesive system with sitespecific drug delivery.8) It is necessary to design a drug delivery system that could not only curtail and alleviate the shortcomings of conventional drug delivery vehicles, but also deliver the antimicrobial agent to the infected cell lines.Clarithromycin is the drug of choice to treat peptic ulcer as H. pylori resistance rate is much lower for clarithromycin as compared to other antibiotics like amoxicillin and tetracycline. Stomach-specific antibiotic drug delivery would be highly beneficial in the treatment of H. pylori infection in peptic ulcer disease. 9) Clarithromycin is having good stability in a gastric pH.10) The low density hydroxypropyl methylcellulose (HPMC) polymers have good bio-adhesive property. Polysaccharides like chitosan and gum acacia was found to float but not much promising like oils.11) Thus incorporation of oil in the drug delivery system with the Alg-HPMC beads shows good floating and muco-adhesion property.12)The present work describes incorporation of an active component known to be effective against H. pylori, clarithromycin, into alginate (Alg)-Ca and Alg-HPMC beads and reports the release of drug from the beads in an acidic environment and also applies the new approach of mucoadhesive and floating for synergistic effect. Experi...