In order to understand the role of the formulation components in topical drug delivery it is necessary to separate the various contributing factors, these include thermodynamic activity effects, changes in the ionisation state of the permeant and alteration of the membrane properties. Three model permeants, ibuprofen, salicylic acid and acetaminophen were selected to represent a range of physicochemical properties. Solubility and distribution behaviour of ibuprofen and salicylic acid was determined and demonstrated how the addition of cosolvent could impact upon the permeation of the two weak acids by altering the ionisation state of the permeants. The cosolvents, (typical formulation excipients) were water, propylene glycol ethanol, mineral oil, miglyol and Transcutol . To begin with binary combinations were tested, moving on to ternary combinations more representative of an actual formulation. Silicone membranes were used to investigate the diffusional properties of the model permeants. Similarities in the behaviour of the permeants in the selected solvents were observed. Ibuprofen was found to have a higher permeation rate than salicylic acid possibly because of the hydrophobic nature of the Silicone membrane. Analysis of diffusion profiles using a nonlinear curve fitting procedure revealed that the selected vehicles enhanced the permeation of ibuprofen and salicylic acid by increasing partitioning into the membrane. Acetaminophen was found to oxidise in the presence of hydrogen bonding solvents, and for this reason was eliminated from the study. Diffusion experiments were conducted using an established ATR-FTIR approach but the data interpreted using sophisticated chemometric approaches which allowed the deconvolution of the IR signals of all permeating species and the membrane. Using this approach it was possible to examine the individual profiles from multi-component formulations. Using data from traditional diffusion experiments alongside information obtained from ATR-FTIR diffusion experiments using a new method of analysis allowed a deeper insight into the role of the solvent in the permeation process. Data from ATR-FTIR experiments revealed that ethanol permeated silicone membrane at a faster rate than the other solvents studied. This finding was in line with evidence from Franz-type diffusion experiments in which flux was consistently higher from formulations containing ethanol. Where possible, the effect of the same vehicles on the permeability properties of human skin was examined. The vehicles selected were predominantly influencing the partition of the drug into the skin rather than the diffusion coefficient.