Bile salts are bio-compatible natural amphiphiles having a significant role in pharmaceutical field as a solubility and permeability enhancer and possess a great biological importance for release and transport of nutrients due to dynamic micellization behavior. Hence, to unfold the interactional mystery of drug − bile salt system in the field of anti-retroviral drugs, we have aimed to investigate solute–solute and solute–solvent interactions of bile salts (NaC and NaDC) with anti-HIV drugs (Emtricitabine and Lamivudine) by using various techniques like volumetry, compressibility, and viscometry at temperature range (298.15 K-313.15 K) with a regular variation of 5 K. Experimental density and speed of sound data have been used to evaluate various physicochemical parameters such as apparent molar volume (φv), isentropic compressibility (κs), and apparent molar adiabatic compression (φκ). The CMC values of bile salts in pure water and aqueous solution of ECT and LMV at 298.15 K have also been evaluated from speed of sound data which corroborate well with our earlier conductivity study on these surfactants. The trends of φv, κs and φκ values for both NaC and NaDC with temperature and in presence of drugs (ECT/LMV) indicate strong solute–solvent interactions in studied system. The results are elucidated in terms of electrostatic and hydrophilic-hydrophobic interactions in bile salt-drug-water system which is confirmed by co-sphere overlap model. Comparatively, NaC offers strong interactions with both drugs due to more hydrophilic character than NaDC. Similarly, out of ECT and LMV, ECT shows strong solute–solvent interactions with both bile salts due to more hydrophilic character than LMV. Relative viscosity parameter (ηr) determined from viscosity measurements further supports above results. This interactional knowledge of bile salts with ECT and LMV would be beneficial to develop a better mechanism in pharmacy for enhancing efficacy and permeability of anti-HIV drugs by using bile salts as a drug delivery agent.
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