title: Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations.
abstract: Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Chiara
authors.initials: C
authors.lastname: Conti
authors.affiliation: b Department of Life Sciences and Biotechnology , University of Ferrara , Ferrara , Italy .
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Luca
authors.initials: L
authors.lastname: Castrati
authors.affiliation: c Department of Clinical Sciences , University of Parma , Parma , Italy .
authors.forename: Carmelo
authors.initials: C
authors.lastname: Scarpignato
authors.affiliation: d Faculty of Health Sciences , Fernando Pessoa University , Porto , Portugal , and.
authors.forename: Pedro
authors.initials: P
authors.lastname: Barata
authors.affiliation: e Department of Drug Sciences , University of Pavia , Pavia , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sandri
authors.affiliation: e Department of Drug Sciences , University of Pavia , Pavia , Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caramella
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Ruggero
authors.initials: R
authors.lastname: Bettini
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Buttini
authors.affiliation: a Department of Pharmacy , University of Parma , Parma , Italy .
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D017291:Clarithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D000658:Amoxicillin; D017291:Clarithromycin
keywords: Assembled system; drug combination; floating; oral delivery; prolonged release; release module