Floating amoxicillin trihydrate (AmoxT) tablets, used for eradication of Helicobacter pylori (H. pylori), were prepared according to a gas-generating technique to extend the drug residence time in the stomach. The drug release rate from the floating tablets in acidic dissolution medium, in which AmoxT is known to be unstable, was studied using two dissolution techniques: openloop system of the flow-through cell (FTC) and the beaker method. Analysis of AmoxT in the dissolution medium was carried out by UV spectrophotometric and HPLC methods. The comparison indicates that the open-loop system of the FTC, which is based on non-cumulative (fresh) dissolution samples, is the preferred dissolution technique, and in this case, the drug could be analyzed by UV spectrophotometric and HPLC methods. However, in the case of a large number of QC samples, UV spectrophotometry is preferred to the HPLC method, which requires relatively longer time for analysis thereby increasing drug degradation. On the other hand, in the case of the beaker method, which is based on cumulative dissolution samples, the drug must be analyzed by HPLC. Generally, the beaker method is not recommended due to the problems associated with the accumulation of AmoxT degradation product in the dissolution medium. This study describes a simple dissolution method capable of discriminating between different AmoxT gastroretentive formulations without any additional experimental or calculational steps. INTRODUCTION The lifetime risk for developing a peptic ulcer is approximately 10% of the general population (1, 2). H.pylori is one of the major causative agents of peptic ulcer (1). Although many antibacterial agents have a very low minimum inhibitory concentration (MIC) against H.pylori in vitro (3), no single agent is effective in the eradication of the infection in vivo when administered alone (4). In addition, single antibiotic therapy is strongly discouraged to prevent the development of resistant strains (5). There could be one or several reasons for the failure of single-antibiotic therapy against H.pylori. Firstly, the organism resides in the mucus gel close to the acidic environment of the gastric fluid. Many antibacterial agents, such as penicillin and erythromycin, degrade rapidly in acidic medium. Secondly, the drug must diffuse into the mucus layer to furnish concentrations sufficient for antibacterial activity. Lastly, the contact time of antibacterial drugs with the organism needs to be sufficiently long for successful eradication of H.pylori from the gastric mucosa (6), which can be achieved through a gastroretentive drug delivery system (GRDDS). Gastric residence time of an oral dosage form is affected by several factors. To pass through the pyloric valve into the small intestine, the particle size should be in the range of 1–2 mm (7, 8). The rate of gastric emptying depends mainly on viscosity, volume, and caloric content of meals. The nutritive density of meals helps to determine gastric emptying time. It does not make any difference whether the meal has high protein, fat, or carbohydrate content as long as the caloric content is the same. However, an increase in acidity and caloric value slows down gastric emptying time. Biological factors such as age, body mass index (BMI), gender, posture, and diseased states (diabetes, Crohn’s disease) influence gastric emptying. In the case of elderly people, gastric emptying is slowed down. Generally, females have slower gastric emptying rates than males. Stress increases gastric emptying rates while depression slows it down (7, 9, 10). Different drug delivery methods can be used for gastric retention such as floating (11), mucoadhesive, superporous hydrogel, expandable, magnetic, and high-density systems (12). GRDDS is superior for (1) drugs that are locally active in the stomach (e.g., misroprostol, antacids); (2) drugs that have narrow absorption windows in the gastrointestinal tract (GIT) (e.g., L-DOPA, para aminobenzoic acid, furosemide, riboflavin); (3) drugs that are unstable in the intestinal or colonic environment (e.g., captopril, ranitidine HCl, metronidazole); (4) drugs that disturb normal colonic microbes (e.g., antibiotics against H. pylori); and (5) drugs that exhibit low solubility at high pH values (e.g., diazepam, chlordiazepoxide, verapamil HCl) (13). In practice, drugs that are less soluble in a high pH environment require more retention time in the stomach to improve *Corresponding author. e-mail: ashmawya@yahoo.com dx.doi.org/10.14227/DT200113P27