title: Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.
abstract: The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to assess AmB distribution among the lipolysis phases. The duration of lipolysis was comparable among the three formulations except for 2 g load of iCo-009 which had a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components of iCo-009 experienced lower extent of lipolysis as compared to other formulations. Amphotericin B concentration in the aqueous phases was the highest with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels in the undigested lipid layers were comparable between iCo-009 and iCo-010 and were higher than with iCo-011. Given the observation that iCo-010 had the highest aqueous micellar solubilization and the lowest sediment recovery of AmB among the tested formulations, these results could potentially be used to interpret and predict the in vivo performance of AmB- SEDDS formulations in future studies.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3. fady@mail.ubc.ca
authors.forename: Fady
authors.initials: F
authors.lastname: Ibrahim
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
authors.forename: Olena
authors.initials: O
authors.lastname: Sivak
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wasan
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003089:Colipases / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D008823:Micelles; D010194:Pancreatin / Q000378:metabolism; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D003089:Colipases; D004337:Drug Carriers; D008055:Lipids; D008823:Micelles; D000666:Amphotericin B; D010194:Pancreatin