title: Design, Optimization, and Evaluation of a Novel Metronidazole-Loaded Gastro-Retentive pH-Sensitive Hydrogel.
abstract: Floating pH-sensitive chitosan hydrogels containing metronidazole were developed for the eradication of Helicobacter pylori from the stomach. Hydrogels were prepared by crosslinking medium or high molecular weight chitosan in lyophilized solutions containing metronidazole using either citrate or tripolyphosphate (TPP) salts at 1% or 2% concentration. A 23factorial design was developed to study the influence of formulation parameters on the physical characteristics of the prepared hydrogels. The interaction between hydrogel components was investigated. The morphology of the prepared hydrogels was inspected and their percentage swelling, release pattern, and moisture content were evaluated. The results revealed the absence of interaction between hydrogel components and their highly porous structure. Percentage swelling of the hydrogels was much higher, and drug release was faster in gastric pH compared with intestinal pH. The formula prepared using 2% high molecular weight chitosan and 2% TPP significantly swelled (700%) within the first 4 h and released the loaded drug over a period of 24 h. Its moisture content was not affected by storage at high relative humidity. Therefore, this formula was selected to be tested in dogs for its gastric retention (using X-ray radiography) and efficacy in the eradication of H. pylori (using histopathological and microbiological examination). The results revealed that the prepared hydrogel formula was retained in dog stomach for at least 48 h, and it was more effective against H. pylori than the commercially available oral metronidazole tablets (Flagyl®).
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Eini St., 11562, Cairo, Egypt.
authors.forename: Galal M
authors.initials: GM
authors.lastname: El-Mahrouk
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Eini St., 11562, Cairo, Egypt. mona.abouleinien@pharma.cu.edu.eg.
authors.forename: Mona H
authors.initials: MH
authors.lastname: Aboul-Einien
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Eini St., 11562, Cairo, Egypt.
authors.forename: Amal I
authors.initials: AI
authors.lastname: Makhlouf
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008795:Metronidazole / Q000737:chemistry* / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011122:Polyphosphates; D008795:Metronidazole; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; C005692:triphosphoric acid
keywords: chitosan; floating drug delivery system; gastric retention; metronidazole; pH-sensitive swelling