title: Spray freeze drying with polyvinylpyrrolidone and sodium caprate for improved dissolution and oral bioavailability of oleanolic acid, a BCS Class IV compound.
abstract: Spray-freeze-drying (SFD) of oleanolic acid (OA), a BCS Class IV compound, with polyvinylpyrrolidone-40 (PVP-40) as stabilizer and sodium caprate (SC) as wetting agent and penetration enhancer produced kinetically stable, amorphous solid dispersion systems with superior in vitro dissolution performance, and better and more uniform absorption in comparison with commercial OA tablet. Relative to the SC-free formulation, the presence of SC in the formulation resulted in a significant increase in the in vivo absorption rate of OA while exerting no apparent impact on the extent of OA absorption. The SFD-processed OA formulations and commercial OA tablet generally exhibited large inter-animal variability in oral bioavailability, consistent with the absorption characteristics of BCS Class IV compounds. Inclusion of SC coupled with the replacement of OA with its sodium salt (OA-Na) in the formulation was shown to substantially decrease the observed absorption variability. Above results suggested that increases in both dissolution rate and intestinal permeability of BCS Class IV compounds, as exemplified by the SFD-processed dispersion system containing both OA-Na and SC, are critical to reducing the large inter-individual absorption variability commonly observed with this class of drugs.
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao.
authors.forename: Henry H Y
authors.initials: HH
authors.lastname: Tong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Du
authors.forename: Geng Nan
authors.initials: GN
authors.lastname: Wang
authors.forename: H M
authors.initials: HM
authors.lastname: Chan
authors.forename: Qi
authors.initials: Q
authors.lastname: Chang
authors.forename: Leon C M
authors.initials: LC
authors.lastname: Lai
authors.forename: Albert H L
authors.initials: AH
authors.lastname: Chow
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D003652:Decanoic Acids / Q000737:chemistry*; D004304:Dosage Forms; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D009828:Oleanolic Acid / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability; D011205:Povidone / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014906:Wetting Agents / Q000737:chemistry*
chemical_list: D000336:Aerosols; D003652:Decanoic Acids; D004304:Dosage Forms; D005079:Excipients; D014906:Wetting Agents; C031071:decanoic acid; D009828:Oleanolic Acid; D011205:Povidone