Triglycerides mixed

Oils are mixtures of mixed esters with different fatty acids distributed among the ester molecules. Generally, identification of specific esters is not attempted instead the oils are characterized by analysis of the fatty acid composition (8,9). The principal methods have been gas—Hquid and high performance Hquid chromatographic separation of the methyl esters of the fatty acids obtained by transesterification of the oils. Mass spectrometry and nmr are used to identify the individual esters. It has been reported that the free fatty acids obtained by hydrolysis can be separated with equal accuracy by high performance Hquid chromatography (10). A review of the identification and deterrnination of the various mixed triglycerides is available (11). 

It is well appreciated that dietary fat retards proximal gastrointestinal transit. For hydrophobic drugs with low aqueous solubility, dissolution becomes the rate-limiting process the appreciation that fat might increase bioavailability by increasing time available for dissolution and that mixed triglycerides often provide a better solvent than aqueous media has not been lost on formulation scientists. 

Dietary fat consists essentially of mixed triglycerides. These fatty lipids pass through the stomach into the small intestine without much change in structure. In the small intestine, triglycerides are partly hydrolyzed by an enzyme (lipase) that leads to the formation of oil-water emulsion. 

For mixed triglycerides, the name indicates the order in which the fatty acids are arranged. For example, glyceryl palmitooleostearate (Problem 15.2b), glyceryl stearopalmitooleate (Example 15.2) and glyceryl palmitostearooleate (Sec. 15.1) represent three isomeric mixed triglycerides. 

Heron, S. and Tchapla, A. (1994) Choice of stationary phases for separation of mixed triglycerides by liquid phase chromatography. Analusis, 22, 114-126. 

LPL exhibits no fatty acid specificity during hydrolysis of mixed triglycerides but does have strong positional specificity (Morley and Kuksis, 1977). It acts on primary ester bonds with some preference for the sn-1 over the sn-3 position of triglycerides (Somerharju et al., 1978) and can hydrolyze 2-monoglycerides only after their conversion to the sn-1 or sn-3 isomers (Nilsson-Ehle et al., 1973). It shows phospholipase Ai activity on phosphatidyl choline (i.e., it hydrolyzes the primary ester bond at the sn-1 position). This contrasts with most phospholipases A, which exhibit A2 activitiy. 

Figure 26-5. Principle of the 13C-mixed triglyceride breath test. Absorption of 13C-mixed triglycerides requires prior hydrolysis by pancreatic lipase (1), which leads to production of free fatty acids (stearic acid) and monoacylglycerol [2-(l-13C)octanoylglycerol]. These metabolites are incorporated into micelles, absorbed, and transported to the liver (2). Further degradation by hepatic enzymes and P-oxidation results in formation of 13C02, which is absorbed into the bloodstream, transported to the lung, and exhaled (3). Thus, exhalation of 13C02 reflects intestinal lipolysis and is a marker of pancreatic exocrine function.

Vantrappen GR, Rutgeerts PJ, et al. Mixed triglyceride breath test a noninvasive test of pancreatic lipase activity in the duodenum. Gastroenlerol-ogy 96 1126-1134,1989. 

Hagemann, J.W., and J.A. Rothfus, Computer Modeling of Packing Arrangements and Transitions in Saturated-cw-Unsaturated Mixed Triglycerides, Ibid. 69 429-435 (1992). 

Amarri S, Harding M, Coward WA, Evans TJ, Weaver LT. C-mixed triglyceride breath test and pancreatic enzyme supplementation in children with cystic fibrosis. Arch Dis Childhood 1997 76 349-51. 

Loser C, Brauer C, Aygen S, Hennemann O, Folsch UR. Comparative clinical evaluation of the C-mixed triglyceride breath test as an indirect test of pancreatic function. Scand J Gastroenterol 1998 33 327-34,... 

Chief constituents Mixed triglycerides of linoleic, oleic, and other fatty acids. 

The common commercial fats and oils are primarily mixed triglycerides of five common fatty acids palmitic, stearic, oleic, linoleic, and linolenic acids. All are unbranched carboxylic acids and have 18 carbon atoms except for palmitic which has 16 carbon atoms. 

Mixed triglycerides formed by coupling of drugs to diglycerides exhibit physicochemical properties (120) and absorption characteristics (121)similar to those of natural triglycerides, resulting in a different pharmacokinetic and/or pharmacodynamic profile compared to that of the unmodified drug. Such an approach has been used to improve the oral systemic availability of phenytoin (122). 

For several mixed triglycerides, especially those containing unsaturated chains, or chains that all differ in length, other forms of molecular packing can occur. 

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