Noninvasive methods to determine the critical micelle concentration of some bile acid salts

Abstract

In this work the critical micelle concentrations (cmc) of four bile salts, sodium cholate, sodium glycocholate, sodium deoxycholate, and sodium glycodeoxycholate, are determined and presented. Three independent noninvasive methodologies (potentiometry, derivative spectrophotometry, and light scattering) were used for cmc determination, at 25 degrees C with ionic strength adjusted to 0.10 M with NaCl. Spectrophotometric and potentiometric studies of some bile salts were also executed at various ionic strength values, thus allowing the influence of the ionic strength on the cmc value of the bile salt to be assessed. A critical comparison of the cmc values obtained with data collected from the literature is presented. Furthermore, this work makes an evaluation of the conceptual bases of different methodologies commonly used for cmc determination, since variations in the results obtained can be related mainly to different intrinsic features of the methods used (such as sensitivity or the need to include tracers or probes) or to the operational cmc definition applied. The undoubted definition of the experimental bile salt concentration that corresponds to cmc (operational cmc) is essential since in the case of these amphiphiles the formation of micelles is not as abrupt as in the case of ordinary association colloids. The biphasic nature of their aggregation leads to a "round-shaped" variation of the experimental parameters under analysis, which makes difficult the evaluation of the cmc values and can be responsible for the different results obtained.

Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

“…It has been reported that the CMC of NaDC and NaGC at 25°C with ionic strength adjusted to 0.10 M with NaCl was 2.35 and 11.60 mM, respectively (Reis et al, 2004). Therefore, the used bile salt concentrations were much higher than CMC, regardless of ratio, considering that dilution is minimal in the stomach.…”

Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption

“…The mixed micellar system used in this method consisted of a mixture of six bile salts (NaDC, NaC, NaTDC, NaTC, NaGC and NaGDC) which included dihydroxy, trihydroxy, conjugated and unconjugated bile salts with lecithin phospholipid in 0.15 M NaCl with the pH controlled by HEPES buffer at 6.5. The CMC of the mixed micellar system was deemed to be 0.0046 M based on the average value of the CMCs of the bile salts included in the mixture in 0.15 M NaCl [NaTC CMC = 0.004 M (Natalini et al, 2014), NaDC CMC = 0.0024 M (Natalini et al, 2014), NaTDC CMC = 0.0024 M (Natalini et al, 2014), NaC CMC = 0.0075 M (Reis et al, 2004), NaGC CMC = 0.009 M (Natalini et al, 2014) and NaGDC CMC = 0.0022 M (Natalini et al, 2014)]. The bile salt–lecithin mixed micellar solution was used over a concentration range 0.005–0.017 M. The mixed micellar system was prepared in molar ratios similar to that present physiologically (Wiedmann et al, 2002).…”

Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives

“…Spectrophotometry in the absence of exogenous probe molecules has proved to be effective in revealing the formation of low aggregation number BA assemblies [37,38]. The CMC can be identified by monitoring the profile of variation of some intrinsic property of the system (such as Abs max around 195-200 nm of the main characteristic UV band) with the surfactant concentration [37].…”

“…The CMC can be identified by monitoring the profile of variation of some intrinsic property of the system (such as Abs max around 195-200 nm of the main characteristic UV band) with the surfactant concentration [37].…”