Hypothesis
Solubilization is a fundamental process that underpins various technologies in the pharmaceutical and chemical industry. However, knowledge of the location, orientation and interactions of solubilized molecules in the micelles is still limited. We expect all-atom molecular dynamics simulations to improve the molecular-level understanding of solubilization and to enable its in silico prediction.
Methods
The solubilization of six drugs in intestinal mixed micelles composed of taurocholate and dioleoyl phosphatidylcholine was simulated by molecular dynamics in explicit water and measured experimentally by liquid chromatography. The location and orientation of the solubilized drugs were visualized by cumulative radial distribution functions and interactions were characterized by radial distribution function ratios and hydrogen bonding.
Findings
A new simulation-derived parameter was defined, which accounts for drug-micelle and drug-water interactions and correlates (R2 = 0.83) with the experimentally measured solubilization. Lipophilicity was found to govern the location of all drugs in the micelle (hydrophobic core, palisade layer or on the surface), while hydrogen bonding was crucial for orientation and solubilization of two of the molecules. The study demonstrates that explicit, hydrogen bond-forming water molecules are vital for accurate prediction of solubilization and provides a comprehensive framework for quantitative studies of drug location and orientation within the micelles.

The rheological response of surfactant solutions containing a mixture of anionic and zwitterionic surfactants, in the presence of shorter-chain cationic and nonionic co-surfactants and various counterions was studied experimentally and described theoretically by developing the model that accounts for the competitive adsorption of different monovalent and divalent counterions, as well as the inclusion of co-surfactants within the micelles. This model was used to predict the salt curve dependence of systems with various salt and co-surfactant concentrations and was tested against the experimentally measured salt curves. A good agreement was found between the experimental data and the proposed theoretical model. It was demonstrated that the adsorption energies of counterions on the micellar surfaces remain unchanged with the addition of co-surfactants. However, the conditions for micelle branching are significantly affected, particularly in the presence of divalent and trivalent counterions. The presence of co-surfactants reduces the number of adsorbed divalent ions, thereby diminishing their effect on micelle branching.

Emulsification experiments with four silicone oils, having viscosities ranging from 0.01 to 30 Pa.s, were conducted in two types of media: nearly Newtonian polyvinyl alcohol (PVA) solutions and non-Newtonian mixtures induced by worm-like micelles in solutions of sodium laureth sulfate and cocoamidopropyl betaine (BS) with NaCl. The increased viscosity of BS solutions upon the addition of NaCl did not significantly affect the drop size in the formed emulsions. In contrast, the increased viscosity of solutions with higher PVA concentrations significantly reduced the drop sizes for all silicone oils. A theoretical expression predicting the maximum drop size in both types of media (nearly Newtonian and non-Newtonian) was derived and validated against experimental data. The expression accounts for shear-thinning behavior in both the aqueous and oil phases. Interfacial stress dominates the breakage of less viscous oils, while viscous stress inside the breaking drop plays a leading role for more viscous oils. The formation of emulsions with similar sizes in non-Newtonian solutions of BS with different NaCl concentrations was explained by their strongly shear-thinning behavior, which leads to nearly similar viscosity at high shear rates, despite their zero-shear viscosities differing by more than two orders of magnitude.

Micelles formed by bile salts in aqueous solution are important for the solubilization of hydrophobic molecules in the gastrointestinal tract. The molecular level information about the mechanism and driving forces for primary-to-secondary micelle transition is still missing. In the current study, the micelle formation of 50 mM solutions of taurodeoxycholate (TDC) is studied by atomistic molecular dynamics simulations. It is shown that primary micelles with an aggregation number of 8-10 emerge and persist within the first 50 ns. Then, they coalesce to form secondary micelles with an aggregation number of 19 molecules. This transition is governed by hydrophobic interactions, which significantly decrease the solvent-accessible surface area per molecule in the secondary micelles. The addition of monomers of the sodium salt of fatty acids (FAs), as agents aiding hydrophobic drug delivery, to secondary TDC micelles results in the co-existence of mixed FA-TDC and pure FA micelles. The studied saturated FAs, with chain lengths of C14:0 and C18:0, are incorporated into the micelle core, whereas TDC molecules position themselves around the FAs, forming a shell on the micelle surface. In contrast, the tails of the C18:1 unsaturated fatty acid mix homogeneously with TDC molecules throughout the entire micelle volume. The latter creates a very suitable medium for hosting hydrophobic molecules in the micelles containing unsaturated fatty acids.

The primary objective of this study is to determine the similarities and differences in the surface, film, and foam properties of alkyl sucrose esters (SEs) with high monoester content (≥ 70 %) and polyoxyethylene alkyl ethers (Brijs) with a high number of ethoxy groups (≥ 20) in their head group. Experiments were conducted using surfactant molecules with alkyl chain lengths of 12, 16, and 18 carbon atoms at concentrations between 0.01 and 1 wt%, within a temperature range of 25 °C to 60 °C.
The lag time for surfactant adsorption increased with surfactant chain length, decreased with temperature, and significantly decreased with surfactant concentration for both types of studied surfactants. However, increasing the chain length from 12 to 18 carbon atoms led to a 10-fold increase in lag time for Brijs and more than a 600-fold increase for SEs. This effect rendered longer-chain SEs incapable of forming voluminous foam in Bartsch test and led to pronounced coalescence between the bubbles after their separation from the sparger in the foam rise method, resulting in foams with very large bubbles, which exhibited lower stability. The utilization of a Kenwood mixer for foam generation provided sufficient time for longer-chain SE molecules to adsorb on the bubble surfaces and to produce voluminous foams with small bubbles, which remained stable even at 60 °C. In contrast, foams generated from Brijs solutions are very unstable at 60 °C. The long-standing stability of SEs foam was attributed to the formation of mixed mono- and diesters adsorption layers on the bubble surfaces.