Fatty acid, solubilization

Mixed micelles consist of fatty acids solubilized by surfactants or bile salts. The effects of mixed micelles on drug absorption were reviewed by Muranishi Mixed micelles are effective absorption enhancers for compounds such as heparin, streptomycin, gentamycin, and insulin. The effect of mixed micelles on drug absorption tends to be greater at the distal region of the GI tract. The mechanism for increased absorption is not known. Some publications claim that they are safe to use. Others report a disordering effect on intestinal epithelial cells. 

Polyglycerol esters of fatty acids solubilizer, controlled-release tablets... 

Typically, soHd stabilizers utilize natural saturated fatty acid ligands with chain lengths of Cg—C g. Ziac stearate [557-05-1/, ziac neodecanoate [27253-29-8] calcium stearate [1592-23-0] barium stearate [6865-35-6] and cadmium laurate [2605-44-9] are some examples. To complete the package, the soHd products also contain other soHd additives such as polyols, antioxidants, and lubricants. Liquid stabilizers can make use of metal soaps of oleic acid, tall oil acids, 2-ethyl-hexanoic acid, octylphenol, and nonylphenol. Barium bis(nonylphenate) [41157-58-8] ziac 2-ethyIhexanoate [136-53-8], cadmium 2-ethyIhexanoate [2420-98-6], and overbased barium tallate [68855-79-8] are normally used ia the Hquid formulations along with solubilizers such as plasticizers, phosphites, and/or epoxidized oils. The majority of the Hquid barium—cadmium formulations rely on barium nonylphenate as the source of that metal. There are even some mixed metal stabilizers suppHed as pastes. The U.S. FDA approved calcium—zinc stabilizers are good examples because they contain a mixture of calcium stearate and ziac stearate suspended ia epoxidized soya oil. Table 4 shows examples of typical mixed metal stabilizers. 

The typical SEA process uses a manganese catalyst with a potassium promoter (for solubilization) in a batch reactor. A manganese catalyst increases the relative rate of attack on carbonyl intermediates. Low conversions are followed by recovery and recycle of complex intermediate streams. Acid recovery and purification involve extraction with caustic and heat treatment to further decrease small amounts of impurities (particularly carbonyls). The fatty acids are recovered by freeing with sulfuric acid and, hence, sodium sulfate is a by-product. 

Natural mbber usually contains sufficient levels of naturally occurring fatty acids to solubilize the zinc salt. However, if these fatty acids are first extracted by acetone, the resultant "clean" natural mbber exhibits a much lower state of cure. Therefore, to ensure consistent cure rate, fatty acids are usually added. Synthetic mbbers, especially the solution polymers, do not contain fatty acids and requite thein addition to the cure system. 

Sulfenamide accelerators generally requite less fatty acid because they release an amine during the vulcanization process which acts to solubilize the zinc. Guanidines and similar amine accelerators also serve to both activate and accelerate vulcanization. 

A major pharmaceutical use of poly(oxyethylene) sorbitan fatty acid esters is in the solubilization of the oil-soluble vitamins A and D. In this way, multivitamin preparations can be made which combine both water- and oil-soluble vitamins in a palatable form. 

Emulsions of fatty- and petroleum-based substances, both oils and waxes, of the o/w type are made by using blends of sorbitan fatty esters and their poly(oxyethylene) derivatives. Mixtures of poly(oxyethylene(20)) sorbitan monostearate (Polysorbate 60) and sorbitan monostearate are typical examples of blends used for lotions and creams. Both sorbitan fatty acid esters and their poly(oxyethylene) derivatives are particularly advantageous in cosmetic uses because of their very low skin irritant properties. Sorbitan fatty ester emulsifiers for w/o emulsions of mineral oil are used in hair preparations of both the lotion and cream type. Poly(oxyethylene(20)) sorbitan monolaurate is useflil in shampoo formulations (see Hairpreparations). Poly(oxyethylene) sorbitan surfactants are also used for solubilization of essential oils in the preparation of colognes and after-shave lotions. 

Carboxylic Acid Esters. In the carboxyflc acid ester series of surfactants, the hydrophobe, a naturally occurring fatty acid, is solubilized with the hydroxyl groups of polyols or the ether and terminal hydroxyl groups of ethylene oxide chains. 

At room temperature, ca 60 wt % ethylene oxide is needed to solubilize the fatty acids. Surface activity of the ethoxylates is moderate and less than that of alcohol or alkylphenol ethoxylates (84). The ethoxylates are low foamers, a useful property in certain appHcations. Emulsification is the most important function. Its importance is reflected in the wide range of lipophilic solubiHties available in the commercial products. Like all organic esters, fatty acid ethoxylates are susceptible to acid and alkaline hydrolysis. 

Typical commercial ethoxylated sorbitan fatty acid esters are yellow Hquids, except tristearates and the 4- and 5-mol ethylene oxide adducts which are light tan soHds. These adducts, as well as the 20-mol adducts of the triesters, are insoluble but dispersible in water. The monoester 20-mol adducts are water soluble. Ethoxylated sorbitan esters are widely used as emulsifiers, antistatic agents, softeners, fiber lubricants, and solubilizers. In combination with the unethoxylated sorbitan esters or with mono- or diglycetides, these are often used as co-emulsrfiers. The ethoxylated sorbitan esters are produced by beating sorbitan esters with ethylene oxide at 130—170°C in the presence of alkaline catalysts. 

Enzyme—Heat—Enzyme Process. The enzyme—heat—enzyme (EHE) process was the first industrial enzymatic Hquefaction procedure developed and utilizes a B. subtilis, also referred to as B. amjloliquefaciens, a-amylase for hydrolysis. The enzyme can be used at temperatures up to about 90°C before a significant loss in activity occurs. After an initial hydrolysis step a high temperature heat treatment step is needed to solubilize residual starch present as a fatty acid/amylose complex. The heat treatment inactivates the a-amylase, thus a second addition of enzyme is required to complete the reaction. 

The principal mbbers, eg, natural, SBR, or polybutadiene, being unsaturated hydrocarbons, are subjected to sulfur vulcanization, and this process requires certain ingredients in the mbber compound, besides the sulfur, eg, accelerator, zinc oxide, and stearic acid. Accelerators are catalysts that accelerate the cross-linking reaction so that reaction time drops from many hours to perhaps 20—30 min at about 130°C. There are a large number of such accelerators, mainly organic compounds, but the most popular are of the thiol or disulfide type. Zinc oxide is required to activate the accelerator by forming zinc salts. Stearic acid, or another fatty acid, helps to solubilize the zinc compounds. 

Figure 27.1 A soap micelle solubilizing a grease particle in water. An electrostatic potential map of a fatty acid carboxylate shows how the negative charge is located in the head group.

FIG. 1 Critical micelle concentration as a function of the number of carbon atoms in the hydrophobic rest of sodium a-sulfo fatty acid methyl esters. Methods O, surface tension +, conductivity A, solubilization of a dye x, solubility (all without electrolyte) , surface tension with a constant electrolyte concentration of 5 x 10"2 mol/L. (From Ref. 57.)... 

The free fatty acids (FFA, nonesterified fatty acids, im-esterified fatty acids) arise in the plasma from hpolysis of triacylglycerol in adipose tissue or as a result of the action of hpoprotein hpase during uptake of plasma tri-acylglycerols into tissues. They are found in combination with albumin, a very effective solubilizer, in concentrations varying between 0.1 and 2.0 ieq/mL of plasma. Levels are low in the ftiUy fed condition and rise to 0.7-0.8 leq/mL in the starved state. In uncontrolled diabetes mellitus, the level may rise to as much as 2 Ieq/mL. 

Fatty acids can be compared with detergents and have the capacity, i.e, in the form of micelles to solubilize organic material. 

The substrate for the reaetion is triaeylglyeerol of polyunsaturated fatty acid, which is not soluble in water, but can be solubilized with high concentration in octane. The lipase converts its substrate at the interface between octane and the aqueous phase. The free fatty acid produced is poorly water soluble. 

Conversely, the racemic film system appears to be solubilized by the achiral fatty acid component. At compositions of 10-33% palmitic acid, the ESP of the racemic system varies linearly with film composition, indicating that the monolayer in equilibrium with the racemic crystal is a homogeneous mixture of racemic SSME and palmitic acid. At compositions of less than 33% palmitic acid, the ESP is constant, indicating that three phases consisting of palmitic acid monolayer domains, racemic SSME monolayer domains, and racemic SSME crystals exist in equilibrium at the surface. 

Fig. 4-11). Interestingly, the larger amounts of P2 protein that are in myelin of some species correlate with increased widths of the major dense lines as determined by X-ray diffraction, and there appears to be substantially more P2 in large sheaths than small ones [4]. The large variation in the amount and distribution of the protein from species to species and sheath to sheath raises so far unanswered questions about its function. Its similarities to cytoplasmic proteins in other cells, whose functions appear to involve solubilization and transport of fatty acids and retinoids, suggest that it might function similarly in myelin assembly or turnover, but there is currently no direct experimental evidence to support this hypothesis. 

Detergents act as emulsifiers, breaking the oil into tiny droplets, each suspended in water. The disruption of the oil film allows the dirt particles to become solubilized (they peptize). Soap, the sodium or potassium salt of long-chain fatty acids, is a good detergent, although it often forms insoluble compounds with certain salts found in hard water, thus diminishing its effectiveness. 

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