title: The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.
abstract: The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Zur
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Cohen
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Riad
authors.initials: R
authors.lastname: Agbaria
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address: arikd@bgu.ac.il.
authors.forename: Arik
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000818:Animals; D001702:Biopharmaceutics; D018938:Caco-2 Cells; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005913:Glipizide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008567:Membranes, Artificial; D008790:Metoprolol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010539:Permeability; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D008567:Membranes, Artificial; D008790:Metoprolol; D005913:Glipizide
keywords: BCS classification; Controlled-release dosage form; Intestinal permeability; Regioselective absorption; Segmental-dependent permeability