Bile salts, solubility

B) The bile salt solubility in the lumen is a critical factor. 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

FIGURE 25.41 Cholic acid, a bile salt, is synthesized from cholesterol via 7o -hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents. 

Certain surface-active compounds [499], when dissolved in water under conditions of saturation, form self-associated aggregates [39,486-488] or micelles [39,485], which can interfere with the determination of the true aqueous solubility and the pKa of the compound. When the compounds are very sparingly soluble in water, additives can be used to enhance the rate of dissolution [494,495], One can consider DMSO used in this sense. However, the presence of these solvents can in some cases interfere with the determination of the true aqueous solubility. If measurements are done in the presence of simple surfactants [500], bile salts [501], complexing agents such as cyclodextrins [489 191,493], or ion-pair-forming counterions [492], extensive considerations need to be applied in attempting to extract the true aqueous solubility from the data. Such corrective measures are described below. 

An alternative method to overcome the solubility problem mentioned in the last section is to use bile salts to solubilize lipophilic molecules in the donor wells. Figure 7.51 shows a plot of relative permeability (Pe without bildPe with bile) versus membrane retention, which is related to lipophilicity (Section 7.7.2). As the plot shows, the most lipophilic molecules (carvedilol, propranolol, and verapamil) have attenuated permeabilities (by a factor of 3 in the case of carvedilol). The effective partition coefficient between the PAMPA membrane phase and the aqueous phase containing bile salt micelles [577] is expected to be lower for lipophilic molecules, which should result in lower Pe values. This is evident in the figure. 

SD Mithani, V Bakatselou, CN TenHoor, JB Dressman. Estimation of the increase in solubility of drugs as a function of bile salt concentration. Pharm Res 13 163-167, 1996. 

Wang W, Onnagawa M, Yoshie Y and Suzuki T. 2001. Binding of bile salts to soluble and insoluble dietary fibers of seaweeds. Fish Sci 67 1169-1173. 

Certain compounds are known to achieve higher absorption rates from the GI tract if they are taken with food, and this observation has been linked to their solubilization by bile salts [74], Bile salts, especially those of cholic and deoxycholic acids, have been used to solubilize steroid hormones [75], antibiotics [76], and nonsteroidal antiinflammatory drugs [77]. For example, amphotericin B (an antifungal agent) has been solubilized for parenteral use in micelles composed of sodium desoxycholate [78], As illustrated in Fig. 11, the degree of solubilization of carbamazepine by sodium desoxycholate is minimal below the critical micelle concentration but increases rapidly above this value [79]. At sufficiently high concentrations, when the micelles become saturated in carb-amezepine, the apparent solubility reaches a limiting value approximately seven times the true aqueous solubility in the absence of desoxycholate. 

The pancreatic digestion conditions studied included pH, the method of pH control, and bile salts mixture and concentration. In addition, experiments were run to determine if mineral solubility was affected by enzymatic activity, or only by pH-induced solubility changes. 

Figure 3. Calcium solubility dependence on bile salt preparation and concentration used in in vitro digestion (pH 6.8-6.9). Key ...

The presence of bile salts in the alimentary tract can affect absorption of potential toxicants in a variety of ways, depending on their solubility characteristics. 

Bile flow and secretion are stimulated by fats and certain other foods. Bile salts may enhance or delay absorption depending on whether they form insoluble complexes with drugs or enhance the solubility of agents. 

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