title: Phase I clinical study to select a novel oral formulation for ibandronate containing the excipient sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC).
abstract: The aim of this study was to select a novel oral formulation for ibandronate (IBN, CAS number: 13892619). In four cohorts of 28, 21, 19 and 29 healthy volunteers, the impact of the carrier molecule sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC, CAS number: 203787-91-1) on the bioavailability of IBN was investigated. Within each cohort different oral formulations with one dose of ibandronate (30 mg) and three different ratios of IBN:SNAC (1:5, 1:10 and 1:20) were compared to the approved oral IBN tablet formulations (150 and 50 mg IBN) in a 4-way cross-over design and a one week washout between the administrations. The highest mean IBN exposure was achieved with a capsule formulation containing drug-coated beadlets and an IBN:SNAC ratio of 1:5. AUC(last) and C(max) of IBN were approximately 1.3- and 2.2-fold higher compared to the reference treatment (150 mg IBN without SNAC). Increasing the post-dose fasting duration from 15 to 30 min resulted in a more than 2-fold increase in AUC(last), while superimposable IBN serum concentration-time profiles were achieved after a 30 and 60 min fast. The tolerability of the IBN/SNAC treatments in all cohorts was similar to that in the IBN reference groups and most adverse events (AEs) were of mild to moderate intensity.
authors.affiliation: F Hoffmann-La Roche Ltd., Clinical Pharmacology, Grenzacher Strasse 124, CH-4070 Basel, Switzerland. beate.bittner@email.de
authors.forename: B
authors.initials: B
authors.lastname: Bittner
authors.forename: C
authors.initials: C
authors.lastname: McIntyre
authors.forename: H
authors.initials: H
authors.lastname: Tian
authors.forename: K
authors.initials: K
authors.lastname: Tang
authors.forename: N
authors.initials: N
authors.lastname: Shah
authors.forename: W
authors.initials: W
authors.lastname: Phuapradit
authors.forename: H
authors.initials: H
authors.lastname: Ahmed
authors.forename: H
authors.initials: H
authors.lastname: Chokshi
authors.forename: M
authors.initials: M
authors.lastname: Infeld
authors.forename: N
authors.initials: N
authors.lastname: Fotaki
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.forename: A
authors.initials: A
authors.lastname: Portron
authors.forename: P
authors.initials: P
authors.lastname: Jordan
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002210:Caprylates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D015331:Cohort Studies; D018592:Cross-Over Studies; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006207:Half-Life; D006801:Humans; D000077557:Ibandronic Acid; D008297:Male; D008875:Middle Aged; D012995:Solubility; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D002210:Caprylates; D004164:Diphosphonates; D005079:Excipients; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D000077557:Ibandronic Acid