Formulating poorly soluble drugs with polymers in the form of solid dispersions has been widely used for improving drug dissolution. Endogenous surface-active species present in the gut, such as bile salts, lecithin and other phospholipids, have been shown to play a key role in facilitating lipids and poorly soluble drugs solubilisation in the gut. In this study, we examined the possible occurrence of interactions between a model bile salt, sodium taurocholate (NaTC), and model spray dried solid dispersions comprising piroxicam and Hydroxypropyl Methylcellulose (HPMC), a commonly used hydrophilic polymer for solid dispersion preparation. Solubility measurements revealed the good solubilisation effect of NaTC on the crystalline drug, which was enhanced by the addition of HPMC, and further boosted by the drug formulation into solid dispersion. The colloidal behaviour of the solid dispersions upon dissolution in biorelevant media, with and without NaTC, revealed the formation of NaTC-HPMC complexes and other mixed colloidal species. Cellular level drug absorption studies obtained using Caco-2 monolayers confirmed that the combination of drug being delivered by solid dispersion and the presence of bile salt and lecithin significantly contributed to the improved drug absorption. Together with the role of NaTC-HPMC complexes in assisting the drug solubilisation, our results also highlight the complex interplay between bile salts, excipients and drug absorption.