title: Using measured pKa, LogP and solubility to investigate supersaturation and predict BCS class.
abstract: Ionization, lipophilicity and solubility have a profound influence on the transport properties of drug molecules. We will present an overview of why physicochemical properties are important, before discussing how the properties are related to each other. Findings are based on research in our own laboratories using our commercial instruments and software to measure the pKa, lipophilicity (LogP) and intrinsic solubility (LogS0) of 84 marketed ionizable drugs. In general, the most lipophilic molecules were the least soluble in water. Plots of LogP vs. LogS0 show results for these drugs clustered according to other properties, including melting point, number of H-bond donors and acceptors, ability to supersaturate, and BCS class. Molecules with high melting point tended to have a larger number of H-bond donors and acceptors, and to be less soluble than predicted from their LogP. Molecules with low melting point tended to have little H-bond donor capacity, and tended to be more soluble than predicted from their LogP. Molecules that could form supersaturated solutions tended to have higher melting points, and to be less soluble than predicted from their LogP. Molecules in BCS Classes I-III tended to cluster in different parts of the plot. It is proposed that comparing measured LogP and LogS0 of new molecules with these plots will facilitate a quick assessment of their likely BCS Class.
authors.affiliation: Sirius Analytical Ltd., Riverside, Forest Row Business Park, Forest Row, East Sussex, RH18 5DW, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Box
authors.forename: J E A
authors.initials: JE
authors.lastname: Comer
mesh_terms: D000818:Animals; D001702:Biopharmaceutics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D007477:Ions; D008055:Lipids; D004364:Pharmaceutical Preparations