title: Use of conventional surfactant media as surrogates for FaSSIF in simulating in vivo dissolution of BCS class II drugs.
abstract: The usefulness of selected conventional surfactant media to enhance dissolution of BCS class II drugs similarly to fasted state simulated intestinal fluid (FaSSIF) and to predict the absorption of drugs in vivo was evaluated. Dissolution behavior of danazol (Danol), spironolactone (Spiridon) and N74 (phase I compound) was compared between FaSSIF, containing physiological levels of sodium taurocholate (STC) and lecithin, and dissolution media containing various concentrations of anionic surfactant, sodium lauryl sulfate (SLS) or non-ionic surfactant, polysorbate (Tween) 80. Although these media differed largely in their solubilization ability, micelle size, diffusivity and surface tension, similar dissolution enhancing levels were achieved between FaSSIF and drug-specific concentrations of conventional surfactants. The dissolution enhancement was shown, however, to be important only for danazol and N74, molecules that are characterized by high hydrophobicity. An in vivo pharmacokinetic dog study was carried out with N74. Comparison of observed plasma profiles with simulated profiles obtained using compartmental absorption and transit model (CAT) indicated that 0.1% SLS medium was the best to predict in vivo plasma profiles and pharmacokinetic parameters (C(max) and AUC). This study demonstrates the potential of substituting FaSSIF with more simple and cost-effective conventional surfactant media. Use of in vivo prognostic amounts of synthetic surfactants in dissolution testing could largely assist in industrial drug development as well as in quality control purposes.
authors.affiliation: Division of Pharmaceutical Technology, University of Helsinki, Helsinki, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Lehto
authors.forename: Hanna
authors.initials: H
authors.lastname: Kortejärvi
authors.forename: Anni
authors.initials: A
authors.lastname: Liimatainen
authors.forename: Krista
authors.initials: K
authors.lastname: Ojala
authors.forename: Heli
authors.initials: H
authors.lastname: Kangas
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Veli Pekka
authors.initials: VP
authors.lastname: Tanninen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000042:Absorption; D000818:Animals; D001702:Biopharmaceutics / Q000145:classification; D001826:Body Fluids / Q000737:chemistry / Q000187:drug effects; D003198:Computer Simulation; D003613:Danazol / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D004232:Diuretics / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D004965:Estrogen Antagonists / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D005215:Fasting; D005260:Female; D007422:Intestines / Q000737:chemistry; D008297:Male; D008823:Micelles; D004364:Pharmaceutical Preparations; D011136:Polysorbates / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013148:Spironolactone / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D004232:Diuretics; D004965:Estrogen Antagonists; D008823:Micelles; D004364:Pharmaceutical Preparations; D011136:Polysorbates; D013501:Surface-Active Agents; D013148:Spironolactone; D012967:Sodium Dodecyl Sulfate; D003613:Danazol