Distinct Interfacial Behavior of Bile Salts and Its Interaction with Cetylpyridinium Chloride Cosurfactant at the Air/Water Interface

Bile salts have received considerable interest in pharmaceutical formulations for increased bioavailability of the drug. Peculiar physicochemical properties of bile salts and their interface-specific interactions with cosurfactants are believed to be crucial for such formulations. Here, we have investigated the interfacial properties of sodium deoxycholate (NaDC; bile salt) at the air/water and air/water-cetylpyridinium chloride (CPC; pharmaceutically important cosurfactant) interfaces using vibrational sum frequency generation (VSFG), Raman spectroscopy, and surface tensiometry. VSFG, being an inherently interface-selective technique, provides the vibrational spectra of interfacial molecules without interference from the bulk. To understand the peculiarity of NaDC, parallel VSFG measurements were conducted with a conventional anionic surfactant, sodium dodecyl sulfate (SDS). Surface tension measurement revealed that NaDC is more surface active than SDS. Nevertheless, the interfacial water exhibits a weaker orientational order in the presence of NaDC (0.5 mM) than with SDS (0.5 mM), suggesting a weaker interfacial electric field for the former. We propose that NaDC predominantly exists in the protonated neutral form (DC^- + H⁺ DCH) at the air/water interface, which is contrary to its bulk behavior (intrinsic p<i>K</i>_a ∼ 4.9). The surface charge of the CPC cosurfactant (0.5 mM) is partially neutralized by NaDC (0.5 mM), resulting in a net electric field and oriented water at the air/water-CPC + NaDC interface. In contrast, the air/water-CPC + SDS (0.5 mM each) interface is devoid of a long-range electric field and oriented water, revealing complete neutralization of the surface charge. The amplitude ratio of CH₃ and CH₂ symmetric stretch bands (A_CH3(SS)/A_CH2(SS); obtained from the VSFG spectra) reveals reduced hydrophobic packing of CPC alkyl chains by NaDC but enhanced packing by SDS. This unusual behavior is attributed to the rigid steroid backbone of NaDC and its preferred orientation at the interface, which creates more space among the alkyl chains of CPC, enabling them to adopt loosely packed and flexible conformations.