title: Equilibrium drug solubility measurements in 96-well plates reveal similar drug solubilities in phosphate buffer pH 6.8 and human intestinal fluid.
abstract: This study was conducted to develop a high throughput screening (HTS) method for the assessment of equilibrium solubility of drugs. Solid-state compounds were precipitated from methanol in 96-well plates, in order to eliminate the effect of co-solvent. Solubility of twenty model drugs was analyzed in water and aqueous solutions (pH 1.2 and 6.8) in 96-well plates and in shake-flasks (UV detection). The results obtained with the 96-well plate method correlated well (R(2)=0.93) between the shake-flask and 96-well plates over the wide concentration scale of 0.002-169.2mg/ml. Thereafter, the solubility tests in 96-well plates were performed using fasted state human intestinal fluid (HIF) from duodenum of healthy volunteers. The values of solubility were similar in phosphate buffer solution (pH 6.8) and HIF over the solubility range of 10(2)-10(5)μg/ml. The new 96-well plate method is useful for the screening of equilibrium drug solubility during the drug discovery process and it also allows the use of human intestinal fluid in solubility screening.
authors.affiliation: Division of Pharmaceutical Technology, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), 00014 University of Helsinki, Finland. tiina.heikkila@helsinki.fi
authors.forename: Tiina
authors.initials: T
authors.lastname: Heikkilä
authors.forename: Milja
authors.initials: M
authors.lastname: Karjalainen
authors.forename: Krista
authors.initials: K
authors.lastname: Ojala
authors.forename: Kirsi
authors.initials: K
authors.lastname: Partola
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001647:Bile Acids and Salts; D001826:Body Fluids; D002021:Buffers; D004386:Duodenum; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D010743:Phospholipids; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D002021:Buffers; D004364:Pharmaceutical Preparations; D010710:Phosphates; D010743:Phospholipids