The rational design of dermatological formulations

Watkinson, Rebecca Mary (2005) The rational design of dermatological formulations. PhD thesis, University of Greenwich.

Abstract

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 TranscutolTM. 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 non-linear 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.

Data from ATR-FTIR experiments revealed that ethanol permeated silicone membrane at a faster rate than the other solvents studied. This finding was inline 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.

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