title: Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori.
abstract: The aim of this study was to design a local, floating, mucoadhesive drug delivery system containing metronidazole for Helicobacter pylori eradication. Face-centered central composite design (with three factors, in three levels) was used for evaluation and optimization of in vitro floating and dissolution studies. Sodium alginate (X1), low substituted hydroxypropyl cellulose (L-HPC B1, X2) and sodium bicarbonate (X3) concentrations were the independent variables in the development of effervescent floating tablets. All tablets showed acceptable physicochemical properties. Statistical analysis revealed that tablets with 5.00% sodium alginate, 38.63% L-HPC B1 and 8.45% sodium bicarbonate content showed promising in vitro floating and dissolution properties for further examinations. Optimized floating tablets expressed remarkable floating force. Their in vitro dissolution studies were compared with two commercially available non-floating metronidazole products and then microbiologically detected dissolution, ex vivo detachment force, rheological mucoadhesion studies and compatibility studies were carried out. Remarkable similarity (f1, f2) between in vitro spectrophotometrically and microbiologically detected dissolutions was found. Studies revealed significant ex vivo mucoadhesion of optimized tablets, which was considerably increased by L-HPC. In vivo X-ray CT studies of optimized tablets showed 8h gastroretention in rats represented by an animation prepared by special CT technique.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, Hungary. Electronic address: peter.dios@aok.pte.hu.
authors.forename: Péter
authors.initials: P
authors.lastname: Diós
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Nagy
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, Hungary.
authors.forename: Szilárd
authors.initials: S
authors.lastname: Pál
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, Hungary.
authors.forename: Tivadar
authors.initials: T
authors.lastname: Pernecker
authors.affiliation: Department of Microbiology, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Kocsis
authors.affiliation: CROmed Translational Research Centers, Baross Str. 91-95, H-1047 Budapest, Hungary; Department of Public Health Medicine, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Budán
authors.affiliation: CROmed Translational Research Centers, Baross Str. 91-95, H-1047 Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Horváth
authors.affiliation: CROmed Translational Research Centers, Baross Str. 91-95, H-1047 Budapest, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Szigeti
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Bölcskei
authors.affiliation: CROmed Translational Research Centers, Baross Str. 91-95, H-1047 Budapest, Hungary.
authors.forename: Domokos
authors.initials: D
authors.lastname: Máthé
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Dévay
mesh_terms: D000268:Adhesiveness; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006603:Hexuronic Acids / Q000737:chemistry; D007700:Kinetics; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013607:Tablets
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D005079:Excipients; D006603:Hexuronic Acids; D013607:Tablets; D008795:Metronidazole; D020723:Glucuronic Acid
keywords: Ex vivo mucoadhesion; Floating force; Gastroretention; Low substituted hydroxypropyl cellulose; Sodium alginate; X-ray CT imaging