title: Solubility parameter and oral absorption.
abstract: The solubility parameter (delta) for a series of structurally diverse compounds was determined using a group contribution method devised by Fedors, and then related to the degree of oral absorption. Solubility parameter values around 22.5 MPa1/2 were shown to be associated with compounds that were well absorbed, whereas, compounds with a high delta (30-40 MPa1/2) showed poor absorption. A correlation was also evident between the number of H-bonding acceptor groups in a compound and the extent of oral absorption. Surprisingly, when C Log P values were used in comparison, no obvious correlation existed. The conclusion from this work is that the solubility parameter may be a more reasonable predictor of absorption than using C Log P values.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. luigi_g_martini@sbphrd.com
authors.forename: L G
authors.initials: LG
authors.lastname: Martini
authors.forename: P
authors.initials: P
authors.lastname: Avontuur
authors.forename: A
authors.initials: A
authors.lastname: George
authors.forename: R J
authors.initials: RJ
authors.lastname: Willson
authors.forename: P J
authors.initials: PJ
authors.lastname: Crowley
mesh_terms: D000042:Absorption; D000818:Animals; D002626:Chemistry, Pharmaceutical; D006801:Humans; D051379:Mice; D009061:Mouth Mucosa / Q000378:metabolism*; D010599:Pharmacokinetics; D011898:Ranidae; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D013552:Swine