A Study into the Enhancement of Solubility through Surfactants using Chromatography and Calorimetry

Surfactants, such as Tween 20, Tween 80, Etocas 35, Croduret 40, Crodasol HS HP, SDS and Brij 35 are routinely used within the healthcare and pharmaceutical industry to enhance solubility. This work focuses on analysing the aforementioned surfactants, with Tween 20 and Tween 80 each considered at three purity levels with four model compounds, across the critical micellar concentration (CMC) range for each surfactant in addition to determining the CMC of Tween 20, Tween 80, Etocas 35, Croduret 40 and Crodasol HS HP. Such data is of interest to investigate the influence of micelle formation upon compound-polysorbate interaction. three analytical techniques were utilised, namely spectroscopic solubility determination, micellar liquid chromatography (MLC) and isothermal titration calorimetry (ITC). In all cases it was apparent that the maximum solubility for all four compounds increased substantially at concentrations greater than the CMC and that, in most cases, a different retention profile was observed using MLC once the CMC had been exceeded. This thesis is the first to have used such techniques to investigate the behaviour of these polysorbates over a series of concentrations and three levels of polysorbate purity. The findings indicate that the solubilisation potential of polysorbates differs once the CMC has been surpassed and is dependent upon the level of purity selected, i.e. compound-surfactant interactions are partially a consequence of the presence of micelles rather than monomer as well as polysorbate purity. This thesis also investigates the micellisation process for each of the aforementioned surfactants using isothermal titration calorimetry, thus avoiding issues regarding precision found with other techniques. Furthermore, this methodology has not previously been applied to this group of surfactants. For the most commonly used non-ionics (Tween 20 and Tween 80) a further study was undertaken to consider the influence of surfactant purity on the CMC determined. Such information regarding the CMC event is useful from a formulation perspective as it can ensure that the most optimum concentration of surfactant is included within a formulation to maximise its efficacy.