Cholesterol dissolution

I. Corrigan, C. C. Su, W. 1. Higuchi, and A. F. Hofmann, Mesophase formation during cholesterol dissolution in ursodeoxycholic-lecithin solution New mechanism for gallstone dissolution in humans, J.Pharm.Sci., 69 869 (1981). 

Gallstones. Bile acids keep cholesterol soluble in gallbladder bile. Therefore, they are used for the dissolution of cholesterol gallstones. Initial treatment... 

The interfacial barrier theory is illustrated in Fig. 15A. Since transport does not control the dissolution rate, the solute concentration falls precipitously from the surface value, cs, to the bulk value, cb, over an infinitesimal distance. The interfacial barrier model is probably applicable when the dissolution rate is limited by a condensed film absorbed at the solid-liquid interface this gives rise to a high activation energy barrier to the surface reaction, so that kR kj. Reaction-controlled dissolution is somewhat rare for organic compounds. Examples include the dissolution of gallstones, which consist mostly of cholesterol,... 

Various novel imprinting techniques have also been presented recently. For instance, latex particles surfaces were imprinted with a cholesterol derivative in a core-shell emulsion polymerization. This was performed in a two-step procedure starting with polymerizing DVB over a polystyrene core followed by a second polymerization with a vinyl surfactant and a surfactant/cholesterol-hybrid molecule as monomer and template, respectively. The submicrometer particles did bind cholesterol in a mixture of 2-propanol (60%) and water [134]. Also new is a technique for the orientated immobilization of templates on silica surfaces [ 135]. Molecular imprinting was performed in this case by generating a polymer covering the silica as well as templates. This step was followed by the dissolution of the silica support with hydrofluoric acid. Theophylline selective MIP were obtained. 

In the bile cholesterol is kept soluble by fats, phospholipids like lecithin and by bile acids. The important bile acids in human bile are cholic acid, chen-odeoxycholic acid or chenodiol and ursodeoxycholic acid or ursodiol. Bile acids increase bile production. Dehydrocholic acid, a semisynthetic cholate is especially active in this respect. It stimulates the production of bile of low specific gravity and is therefore called a hydrocholeretic drug. Chenodiol and ursodiol but not cholic acid decrease the cholesterol content of bile by reducing cholesterol production and cholesterol secretion. Ursodiol also decreases cholesterol reabsorption. By these actions chenodiol and ursodiol are able to decrease the formation of cholesterolic gallstones and they can promote their dissolution. 

During a Dissolution of Cholesterol Monohydrate in Glycochenodeoxycholate-Glycoursodeoxycholate-Lecithin Solutions and Calcium Carbonate Solubility in Their Solutions... 

Glycochenodeoxycholate cuid glycoursodeoxycholate are known to reduce the cholesterol saturation in bile and to irxiuce the dissolution of cholesterol gallstones in humans.1/2,3)... 

In general, GUDC is known to produce a mesophase during dissolution of cholesterol(CHL) in the presence of lecithin(EL) in vitro, eind then increases the dissolution rate of CHL ty the mesophase formation. However, the effect is less than that of GCDC in vivo. 

The bioavailability of silibinin from the extract is low and seems to depend on several factors such as (i) the content of accompanying substances with a solubilizing character such as other flavonoids, phenol derivatives, aminoacids, proteins, tocopherol, fat, cholesterol, and others found in the extract and (ii) the concentration of the extract itself (132,133). The systemic bioavailability can be enhanced by adding solubilizing substances to the extract (11,134). The bioavailability of silibinin can also be enhanced by the complexation with phosphatidylcholine or p-cyclodextrin, and possibly by the choice of the capsule material (135-137). The variations in content, dissolution, and (oral) bioavailability of silibinin between different commercially available silymarin products—despite the same declaration of content—are significant (138). 

The solubility of cholesterol in bile is determined by the relative proportions of bile acids, lecithin, and cholesterol. Although prolonged ursodiol therapy expands the bile acid pool, this does not appear to be the principal mechanism of action for dissolution of gallstones. Ursodiol decreases the cholesterol content of bile by reducing hepatic cholesterol secretion. Ursodiol also appears to stabilize hepatocyte canalicular membranes, possibly through a reduction in the concentration of other endogenous bile acids or through inhibition of immune-mediated hepatocyte destruction. 

It is generally believed that the mechanism of bioavailability enhancement by CD complexation is through solubility and dissolution rate improvement. However, it should be also noted that CDs might also alter the lipid barrier of the absorption site, which may contribute to the enhanced drug absorption. This effect of CDs on the lipid barrier can be attributed to CDs ability to form complexes with membrane components such as cholesterol, phospholipids, and proteins (Nakanishi et al., 1992). Jambhekar et al. (2004) compared the solubilizing effeqte D, HP-ft-CD, and H -CD on IM. 

Petroni ML, Jazrawi RP, Pazzi P, et al. Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones a randomized multicentre trial. The British-Italian Gallstone Study group. Aliment Pharmacol Ther. 2001 15 123-128. 

The solubilization phenomenon, which refers to the dissolution of normally insoluble or only slightly soluble compounds in water caused by the addition of surfactants, is one of the most striking effects encountered for surfactant systems. Solubilization is of considerable physico-chemical interst, such as in discussion of the structure and dynamics of micelles and of the mechanism of enzyme catalysis, and has numerous practical applications, such as in detergency, in pharmaceutical preparations and in micellar catalysis. In biology, solubilization phenomena are most significant, e.g., cholesterol solubilization in phospholipid bilayers and fat solubilization in fat digestion and transport. 

Some works were reported in which thermosensitive polymers were conjugated with hydrophobic groups. End-capping random poly(NIPA-co-dimethylacrylamide) [55] and grafting poly(NIPA-co-hydroxymethylacryl-amide) [56] with cholesterol moieties led to self-associating polymers with different morphologies. By dissolution of the copolymers in dimethylfor-... 

To purify your product, recrystallize your collected solid from acetone. To accomplish this, transfer the solid to a 125-mL flask. Add a small amount (20 ruL to start) of acetone and a stir bar. Heat to fully dissolve the solid. Add small amounts of acetone, order 1 ruL at a time, as needed, to aid in the dissolution. When solid is dissolved, remove from heat. Cool with the aid of an ice bath. Crystals should form. If they do not, try scratching the inside of the flask with a glass rod. Or, boil off some solvent and recool. Remove these crystals by suction filtration just as you did to collect your impure product. Wash these crystals with a cold 5 ruL portion of acetone and allow them to dry on the filter paper. Transfer to a preweighed vial. Calculate yield of cholesteryl nonanoate from cholesterol and calculate the conversion of cholesterol to cholesteryl nonanoate. 

---