title: Slow release of tetracycline from a mucoadhesive complex with sucralfate for eradication of Helicobacter pylori.
abstract: Treatment composed of a gastric mucoadhesive antibiotic with slow release drug delivery is expected to be effective for the eradication of Helicobacter pylori (H. pylori). In this study, we evaluated the slow release property of the tetracycline-sucralfate acidic complex. Tetracycline was the antibiotic selected because of its complexation capacity with sucralfate. Sustained release was tested using two different dissolution test methods: paddle and flow-through cell. The adhesive paste formed from the acidic complex displayed a longer sustained release profile of tetracycline using flow-through cell method. The milder conditions of the flow-through cell method better mimicked the fasted state of the stomach, suggesting that the oral administration with fasting is appropriate for the acidic complex. Furthermore, the paste formation protected the tetracycline from decomposition under an acidic condition, which apparently contributes to long-term release. Change in the zeta potential of the acidic complex particles was helpful in clarifying the release mechanisms of the tetracycline. The data indicated that the immediate release of tetracycline in the early stage of the test was indispensable to the subsequent paste formation that enables slow release. If administrated orally with fasting, the acidic complex rapidly adheres to the gastric mucosa and sustains long-term release of the tetracycline to the gastric lumen or mucus layer. This antibiotic delivery mechanism, which requires only a minimum dosage, may be effective for efficient eradication of H. pylori.
authors.affiliation: Discovery Platform Technology Department, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. higosui@chugai-pharm.co.jp
authors.forename: Shoichi
authors.initials: S
authors.lastname: Higo
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hino
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D000268:Adhesiveness; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002248:Carbon Monoxide / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004563:Electrochemistry; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D009092:Mucous Membrane; D012995:Solubility; D013392:Sucralfate / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D013752:Tetracycline / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005765:Gastrointestinal Agents; D013392:Sucralfate; D002248:Carbon Monoxide; D013752:Tetracycline