Fixed-Oil Excipient Monographs: Development of USP Fixed-Oil Reference Standards - Pharmaceutical Technology

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Fixed-Oil Excipient Monographs: Development of USP Fixed-Oil Reference Standards
This article summarizes the development and modernization of the United States Pharmacopeia-National Formulary (USP-NF) fixed-oil excipient monographs. This article contains bonus online-exclusive material.


Pharmaceutical Technology
Volume 37, Issue 4, pp. 102-108

The development of USP general chapters to characterize fixed oils

Fixed oils. The characterization of fixed oils ideally should indicate their chemical composition by identifying and quantifying their components with a high degree of specificity and should determine the physical and chemical properties and potential transformations of the fixed-oil substances as a result of hydrolysis, oxidation, degradation, etc.

A fixed oil is formed from two simple building blocks: glycerin (or glycerol) and fatty acids. Unlike glycerin, which has a fixed structure, fatty acids can exhibit significant variation in their structures. In USP−NF, fatty acids in fixed-oil excipients traditionally are designated as carboxylic acids with hydrocarbon chain lengths ranging from 6 to 24 carbon atoms. The majority of fatty acid constituents in USP−NF fixed-oil excipients have unbranched chains, and they either may be fully saturated or may contain one or more double bonds. Glycerin has three hydroxyl groups with which fatty acids can react, and the resulting products are either monoglycerides (monoacylglycerols), diglycerides (diacylglycerols), or triglycerides (triacylglycerols).


Figure 1: Chemical structure for 1-palmitoyl-2-oleoyl-3-linoleoyl-rac-glycerol—an example of a specific triglyceride
Most fats and oils are composed of triglycerides that differ in their fatty acid composition to a certain extent. Those containing the same fatty acids on all three positions are called simple triglycerides. Most naturally occurring triglycerides are of mixed composition and contain two or three different fatty acids. Other constituents that make up not more than (NMT) 3% of the fats and oils are unsaponifiable matter and a number of acyl lipids (e.g., traces of free fatty acids and monoclycerides and diglycerides).

The simplified nomenclature for unbranched fatty acids specifies the chain length and number of double bonds, separated by a colon. For example the triglyceride in Figure 1 contains the 16-carbon saturated palmitic acid (top), abbreviated as C16:0, the 18-carbon unsaturated oleic acid (middle) with 1 double bond, C18:1, and the 18-carbon unsaturated linoleic acid (bottom) with 2 double bonds, C18:2. The 18-carbon unsaturated linolenic acid with 3 double bonds, C18:3, also is known as an omega-3 polyunsaturated fatty acid.

Generally, the fatty acids in a triglyceride define the properties and characteristics of the molecule. Both the physical and chemical characteristics of fixed oils are influenced by component fatty acids, their proportions, and the way in which these are positioned on the glycerin molecule. In general, only the straight, even-numbered chains are present although fats and oils of animal origin can contain both odd-numbered and branched chain fatty acids as well.

Even though the building blocks are limited to glycerin and fatty acids, a large number of different triglycerides can be obtained from them. Thus, in general, a typical oil is a complex mixture of various triglycerides.


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