title: Gastroretentive Accordion Pill: Enhancement of riboflavin bioavailability in humans.
abstract: The purpose of this study was to evaluate the ability of the Accordion Pill (AP), a novel controlled release gastroretentive unfolding dosage form (DF), to increase the bioavailability of riboflavin (RF) in humans. Three formulations containing 75 mg of RF and differing in release rate (immediate release (IR) capsule, AP#1, and AP#2) were administered with a low-calorie meal. Gastric residence time (GRT) of the AP was assessed by magnetic resonance imaging. Serial blood and urine samples were taken and assayed for RF. The AP demonstrated prolonged (up to 10.5 h) GRT in humans. Significant elevation in RF bioavailability (209+/-37%, mean+/-S.E.) was achieved by the AP#1 in comparison to the IR capsule. A correlation was established between the in-vitro release rates from DF and bioavailability of RF in humans, and it was modeled taking into account the saturable nature of RF absorption transport and its narrow absorption window (NAW) in the upper gastro-intestinal tract. It is anticipated that the AP will provide a valuable pharmaceutical solution to enhance therapy with NAW drugs.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kagan
authors.forename: Noa
authors.initials: N
authors.lastname: Lapidot
authors.forename: Michel
authors.initials: M
authors.lastname: Afargan
authors.forename: David
authors.initials: D
authors.lastname: Kirmayer
authors.forename: Eytan
authors.initials: E
authors.lastname: Moor
authors.forename: Yael
authors.initials: Y
authors.lastname: Mardor
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Amnon
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D005260:Female; D052203:Ferrosoferric Oxide; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D005772:Gastrointestinal Transit; D006801:Humans; D007202:Indicators and Reagents; D008279:Magnetic Resonance Imaging; D008297:Male; D012256:Riboflavin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D007202:Indicators and Reagents; D014803:Vitamin B Complex; D012256:Riboflavin; D052203:Ferrosoferric Oxide