Understanding how molecular interactions control the stability of concentrated surfactant formulations and their interactions with lipid membranes

Surfactants are one of the most versatile chemical compounds as it is utilised in a wide range of products and processes such as pharmaceuticals, oil extractions, agrochemicals, food industry, personal care industry and household cleaning products. The use of high levels of surfactants in some of these applications, e.g. detergents, bring about several challenges including, product stability (shelf-life) and physiological safety. Countering these challenges leads to extensive research and development time, enduring high cost, which does not always result in a commercially viable product. The broad aim of this thesis is to address these challenges through understanding the molecular interactions within surfactant formulations involving low temperature stability and also understanding the interactions between these concentrated surfactant solutions with lipid membranes, in the context of ocular irritancy. The effect of changing organic solvent content on the Krafft point of the model surfactant sodium dodecyl sulfate (SDS) was determined through the surface tension pendant drop technique, which proved to be a robust method, and together with the sensitivity and accuracy of X-ray scattering and DSC techniques, the transitions near the solubility boundary of hydrated crystals to lyotropic liquid crystals (and vice-versa) were explored. This enabled SDS phase diagrams to be established for a series of water-glycerol mixtures, identifying and distinguishing between the numerous phases and the conditions under which they form. This knowledge base now provides a platform for understanding the performance of structured, surfactant-based systems, as well as controlling and fine-tuning the route of negative transformations in future studies. Concentrated surfactant formulations also have to comply with health hazard and safety regulations, particularly regarding ocular irritancy. There is a lack of ethical and reproducible eye irritancy test and a need for a better understanding of how surfactant systems interact with lipid membranes. Here, this understanding was gained through examining the permeation and solubility of model membrane, liposomes, by actual detergent formulations and later by surfactant(s) only systems. Through developing a liposome-calcein release assay (LCRA), a meaningful, negative correlation was established between the calcein release (liposome permeation) and corneal swelling, a parameter from the ICE test, suggesting that slow and incomplete solubilisation of lipid membranes leads to higher corneal swelling in the epithelial membrane. To gain a better insight, the three surfactants used in the detergent were tested in various ratios to analyse exclusively their interactions with the lipid bilayer, with the aid of the LCRA and real-time DLS analysis. It was gathered that NI follows the conventional three-stage solubilisation mechanism due to its structure consisting of a large headgroup to tail ratio, while the two anionic surfactants involved interact via a time-limiting flip-flop mechanism. It is proposed that the negative correlation between permeation and ICE test corneal swelling measurements, is due to this prolonged flip-flop mechanism. The LCRA developed provides a high-throughput and a less expensive framework, which shows great promise in developing novel, complimentary assays for predicting ocular irritancy.