title: Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds.
abstract: The diffusion process through a non-porous barrier membrane depends on the properties of the drug, vehicle and membrane. The aim of the current study was to investigate whether a series of oily vehicles might have the potential to interact to varying degrees with synthetic membranes and to determine whether any such interaction might affect the permeation of co-formulated permeants: methylparaben (MP); butylparaben (BP) or caffeine (CF). The oils (isopropyl myristate (IPM), isohexadecane (IHD), hexadecane (HD), oleic acid (OA) and liquid paraffin (LP)) and membranes (silicone, high density polyethylene and polyurethane) employed in the study were selected such that they displayed a range of different structural, and physicochemical properties. Diffusion studies showed that many of the vehicles were not inert and did interact with the membranes resulting in a modification of the permeants' flux when corrected for membrane thickness (e.g. normalized flux of MP increased from 1.25±0.13μgcm(-1)h(-1) in LP to 17.94±0.25μgcm(-1)h(-1)in IPM). The oils were sorbed differently to membranes (range of weight gain: 2.2±0.2% for polyurethane with LP to 105.6±1.1% for silicone with IHD). Membrane interaction was apparently dependent upon the physicochemical properties including; size, shape, flexibility and the Hansen solubility parameter values of both the membranes and oils. Sorbed oils resulted in modified permeant diffusion through the membranes. No simple correlation was found to exist between the Hansen solubility parameters of the oils or swelling of the membrane and the normalized fluxes of the three compounds investigated. More sophisticated modelling would appear to be required to delineate and quantify the key molecular parameters of membrane, permeant and vehicle compatibility and their interactions of relevance to membrane permeation.
authors.affiliation: Department of Pharmacy, Franklin-Wilkins Building, Kings College London, 150 Stamford Street, London, SE1 9NN, United Kingdom; International Pharmaceutical Research Centre, 1-Queen Rania Street, Amman, Jordan.
authors.forename: Omaima N
authors.initials: ON
authors.lastname: Najib
authors.affiliation: Department of Pharmacy, Franklin-Wilkins Building, Kings College London, 150 Stamford Street, London, SE1 9NN, United Kingdom.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
authors.affiliation: Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, United Kingdom.
authors.forename: Stewart B
authors.initials: SB
authors.lastname: Kirton
authors.affiliation: Al-Taqaddom Pharmaceutical Industries Co., 29-Queen Alia Street, Amman, Jordan.
authors.forename: Al-Sayed
authors.initials: AS
authors.lastname: Sallam
authors.affiliation: Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, United Kingdom. Electronic address: d.murnane@herts.ac.uk.
authors.forename: Darragh
authors.initials: D
authors.lastname: Murnane
mesh_terms: D002110:Caffeine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D008567:Membranes, Artificial; D009821:Oils / Q000737:chemistry; D010226:Parabens / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012869:Skin Absorption; D012995:Solubility
chemical_list: D005079:Excipients; D008567:Membranes, Artificial; D009821:Oils; D010226:Parabens; D002110:Caffeine; C038091:butylparaben; C015358:methylparaben
keywords: Cosmetic oils; Dermal drug delivery; Drug transport; Membrane diffusion; Permeation; Physicochemistry