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Title: The effect of oil structure on the diffusion of solutes across synthetic membranes and human epidermis
Author: Najib, Omaima Naji Mahmoud
ISNI:       0000 0004 5368 133X
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2014
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Dermal and transdermal delivery offers a number of potential advantages for drug delivery. However the skin provides an efficient barrier, preventing both excessive water loss from the body and the ingress of xenobiotics. Nevertheless, the vehicle used in the topical formulation can enhance the diffusion of a drug through membranes and reduce the barrier properties. It is hypothesized that oils and oil blends may interact with membranes to different extents depending on the physicochemical properties of the oil(s) and membrane. The aim of this study was to investigate the interaction of oily vehicles with different synthetic membranes (silicone, polyurethane (PU), high density polyethylene (HDPE) and cellulose acetate nitrate (CAN)) and human epidermis with a view to understanding the effect of the co-administration of oil blends on the permeation of model solutes (methyl parabens (MP), butyl parabens (BP) and caffeine (CF)). A gas chromatographic method was developed and validated to quantify the amounts of oil sorbed by silicone membrane (the principal membrane employed). High pressure liquid chromatography was used to quantify the amount of model solute that permeated the membranes contained within Franz diffusion cells. The uptake of different oils (isopropyl myristate (IPM), oleic acid (OA), hexadecane, isohexadecane (IHD) and light liquid paraffin) by the membranes was studied by monitoring the change in weight and thickness of the membranes after immersion in oil. Multivariate analysis (principal component analysis and quantitative structureproperty relationship) was used with a view to identifying the key molecular properties of vehicle components, permeants and the barrier membrane that influenced the permeation of the compounds through different membranes. These mathematical tools were also employed to understand and predict compound permeation across human epidermis from the oily vehicles. The permeation studies of model permeants through silicone membrane and CAN membrane were performed using systems having the same thermodynamic activity. The flux values achieved from different vehicles were different, which indicated vehicle sorption by the membrane potentially altering membrane properties. In solvent uptake studies the buffer showed a greater affinity for the more hydrophilic CAN membrane but induced no swelling of the silicone membrane. The amounts of each oil sorbed by CAN were low; whereas oils were sorbed in different amounts by the hydrophobic membranes. Preferential uptake of one oil over the other component was observed for some blended oil mixtures (for example, this occurred for IHD from OA:IHD blends). Whereas using other blends (for example, those comprising IPM:IHD) both oils entered the membrane in a similar ratio to that applied to the surface. The diffusion of MP from buffer through silicone membrane pre-treated with different oils, showed that as the amount of oil sorbed into silicone membrane increased the diffusion of the subsequently applied MP also increased. Diffusion of the model permeants through different membranes from pure oils showed that oil uptake affected the amount of (model) compound permeated. The highest flux values through human epidermis for all three model permeants were obtained using IHD as a vehicle. Multivariate analysis confirmed that the nature of the vehicle, membrane and permeant affect the permeability of the latter; particularly highlighting the shape of the oil molecule with respect to its uptake into membranes. Oils added into formulations or mixtures are sorbed into the membranes in different amounts. Membrane properties are subsequently modified and the thermodynamic activity of permeant within the formulation is likely to be altered due to preferential oil sorption from the vehicle by the membrane. The flux of the permeants through the membranes was shown to be related to the extent of oil uptake and a complex interaction of physicochemical properties of vehicle, membrane and permeant. The novel approach of using multivariate analysis was found to be promising approach to disassociate the relative importance of the various factors that might influence the interaction and diffusion behaviour of vehicles and permeants with synthetic membranes and human epidermis.
Supervisor: Brown, Marc ; Martin, Gary Peter Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available