The physical, electrophoretic and chromatographic properties (mean diameter, electroosmotic flow, electrophoretic mobility, elution range, efficiency, retention, and hydrophobic, shape, and chemical selectivity) of three surfactant vesicles and one phospholipid vesicle were investigated and compared to a conventional micellar pseudostationary phase comprised of sodium dodecyl sulfate (SDS). Chemical selectivity (solute-pseudostationary phase interactions) was discussed from the perspective of linear solvation energy relationship (LSER) analysis. Two of the surfactant vesicles were formulated from nonstoichiometric aqueous mixtures of oppositely charged, single-tailed surfactants, either cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) in a 3:7 mole ratio or octyltrimethylammonium bromide (OTAB) and SDS in a 7:3 mole ratio. The remaining surfactant vesicle was comprised solely of bis(2-ethylhexyl)sodium sulfosuccinate (AOT) in 10% v/v methanol, and the phospholipid vesicle consisted of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and phosphatidyl serine (PS) in 8:2 mole ratio. The mean diameters of the vesicles were 76.3 nm (AOT), 86.9 nm (CTAB/SOS), 90.1 nm (OTAB/SDS), and 108 nm (POPC/PS). Whereas the coefficient of electroosmotic flow (10(-4) cm2 V(-1) s(-1)) varied considerably (1.72 (OTAB/SDS), 3.77 (CTAB/SOS), 4.05 (AOT), 5.26 (POPC/PS), 5.31 (SDS)), the electrophoretic mobility was fairly consistent (-3.33 to -3.87 x 10(-4) cm2 V(-1) s(-1)), except for the OTAB/SDS vesicles (-1.68). This resulted in elution ranges that were slightly to significantly larger than that observed for SDS (3.12): 3.85 (POPC/PS), 8.6 (CTAB/SOS), 10.1 (AOT), 15.2 (OTAB/SDS). Significant differences were also noted in the efficiency (using propiophenone) and hydrophobic selectivity; the plate counts were lower with the OTAB/SDS and POPC/PS vesicles than the other pseudostationary phases (< or = 75,000/m vs. > 105,000/m), and the methylene selectivity was considerably higher with the CTAB/SOS and OTAB/SDS vesicles compared to the others (ca. 3.10 vs. < or = 2.6). In terms of shape selectivity, only the CTAB/SOS vesicles were able to separate all three positional isomers of nitrotoluene with near-baseline resolution. Finally, through LSER analysis, it was determined that the cohesiveness and hydrogen bond acidity of these pseudostationary phases have the greatest effect on solute retention and selectivity.

A novel oil-in-water microemulsion incorporating the chiral surfactant dodecoxycarbonylvaline (DDCV) was used to achieve the rapid enantiomeric separation of pharmaceutical drugs by electrokinetic chromatography (EKC). Incorporation of DDCV into a microemulsion resulted in an elution range more than double that provided the micellar form of the surfactant aggregate. Interestingly, for the same compounds the enantioselectivity provided by the chiral DDCV microemulsions ranged from 1.06-1.30 for the neutral and cationic drugs, which was slightly higher than that provided by chiral DDCV micelles. The use of a low surface tension oil (ethyl acetate) permitted a much lower concentration of chiral surfactant to be employed; this, together with the use of a zwitterionic buffer (ACES) resulted in a very low conductivity microemulsion that allowed a higher separation voltage to be utilized, resulting in rapid enantiomeric separations (< 8 min.). Mobility matching of the buffer cation(s) was used to improve peak shape and efficiencies. In our limited survey of the phase diagram, the optimum composition of the microemulsion buffer was 1.0% (w/v) DDCV (30 mM), 0.5% (v/v) ethyl acetate, 1.2% (v/v) 1-butanol and 50 mM ACES buffer at pH 7.

Vesicles are large aggregates of surfactant monomers consisting of a spherical bilayer surrounding an internal cavity of solvent. The bilayer structure allows vesicles to be attractive models for the study of various transmembrane and binding processes. The use of thermodynamically stable vesicles (TSV) formed from oppositely charged surfactants for use as a pseudostationary phase in electrokinetic chromatography (EKC) was first accomplished using dodecyltrimethylammonium bromide and sodium dodecyl sulfate (DTAB/SDS). Surfactant vesicles have demonstrated enhanced separation characteristics compared to conventional micelles in EKC, although only investigated in aqueous media. Organic modifiers have been widely studied and used in EKC to enhance separation conditions. In this study, vesicles formed from cetyltrimethylammonium bromide and sodium octyl sulfate (CTAB/SOS) were investigated in the presence of "class I and II" organic modifiers. Electrophoretic and chromatographic parameters were examined as well as linear solvation energy relationship analysis (LSER) to characterize the effects of the modifiers on retention and selectivity in EKC. LSER analysis is a useful way to quantitatively investigate solute/solvent interactions responsible for retention and selectivity.

The chiral surfactant dodecoxycarbonylvaline (DDCV) has proven to be an effective pseudostationary phase for the separation of many enantiomeric pharmaceutical compounds. In this study the elution range and the prediction of octanol-water partitioning for the DDCV micellar system was examined. Through incorporation of DDCV in mixed micelles and unilamellar vesicles, enhancement of the elution range was observed. The mixed micelles contained a second anionic surfactant, sodium dodecyl sulfate (SDS), while the vesicles were composed of DDCV and the cationic surfactant cetyltrimethylammonium bromide (CTAB). Enantioselectivity, as well as other chromatographic and electrophoretic parameters, were compared between the mixed micelles, vesicles, and DDCV micelles. The hydrophobicity of the DDCV system was also evaluated as a predictor of n-octanol-water partition coefficients for 15 beta amino alcohols. The correlation between the logarithm of the retention factor (log k) and log P(ow) for seven hydrophobic beta-blockers and eight beta-agonists were r2 = 0.964 and r2 = 0.814, respectively.

As the pharmaceutical industry continues the daunting search for novel drug candidates, there remains a need for rapid screening methods not only for biological activity, but for physiochemical properties as well. It is invaluable that adequate model systems for absorption and/or bioavailability be developed early in the drug evaluation process to avoid the loss of promising compounds late in development. The focus of this paper is the use of vesicle EKC (VEKC) as a high-throughput, easy, cost-effective, and predictive model for the passive transcellular diffusion of drug candidates in the intestinal epithelium. Vesicles are large aggregates of molecules containing a spherical bilayer structure encapsulating an internal cavity of solvent. It is this bilayer structure that makes vesicles attractive as model membranes. In this study, vesicles were synthesized from both phospholipids and surfactant aggregates, and then employed as pseudostationary phases in EKC (VEKC). The interaction of drug molecules with vesicles in EKC was then used as the basis for an in vitro assay to evaluate passive diffusion. The VEKC technique showed a statistical correlation between the retention of drug candidates using surfactant and phospholipid vesicles and passive diffusion data (log Pow and colon adenocarcinoma). VEKC analysis offers high-throughput capabilities due to the short run times, low sample, and solvent volumes necessary, as well as instrument automation. However, due to the complexity of drug absorption in the intestine, difficulty arises when a single in vitro model is used to predict in vivo absorption characteristics. Therefore, the retention of drug candidates using VEKC in conjunction with other permeability prediction methods can provide a primary screen for a large number of drug candidates early in the drug discovery process with minimal resources.