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

USP general chapter Fats and Fixed Oils <401>. ZUSP general chapter Fats and Fixed Oils <401> includes several test procedures to characterize and determine the properties of fats and fixed oils. During the 2005–2010 revision cycle, <401> underwent several revisions in PF (11–13). Before its proposed revision that appeared in 2008 (11), the chapter contained mostly simple wet chemistry–based methods to measure values characteristic of fats and fixed oils such as Acid Value (Free Fatty Acids), Ester Value, Hydroxyl Value, Iodine Value, and Saponification Value. Essentially, these tests used chemical reactions to quantitatively estimate the selected functional group(s) or to calculate—but not necessarily to identify—the constituents of a fat or oil. Thus Ester Value, Hydroxyl Value, Iodine Value, and Saponification Value traditionally are treated as oil and fat structure index tests. These indices, especially if combined, help to provide a rough idea of the identity of the sample. A triglyceride can be hydrolyzed to fatty acids and glycerin. Thus, Acid Value (Free Fatty Acids) is used as a measure of the degree of an oil’s hydrolysis.

In addition, Peroxide Value, Anisidine Value, and Total Oxidation Value (Totox) also were included in general chapter <401> before the 2008 revision (11). The tests for Anisidine Value and Total Oxidation Value (Totox) were proposed in 2003 (14) to support several monographs that contain polyunsaturated fatty acids, particularly some dietary supplement monographs. Fats and oils containing unsaturated fatty acids are prone to oxidation. Peroxide Value, Anisidine Value, and Total Oxidation Value (Totox) using wet-chemistry principles can reveal the extent of oxidative degradation of fats and fixed oils. Peroxide Value measures the amount of primary oxidation products, such as hydroperoxides, and the Anisidine Value measures secondary products, including aldehydes and ketones. Because the tests can determine the extent of oxidative deterioration, they are useful analytical tools to predict the expected shelf life of a fat or oil and to monitor an oil’s stability.

Before the proposed revision in 2008, <401> also provided tests for Unsaponifiable Matter, Solidification Temperature of Fatty Acids, and Fatty Acid Composition (11). The latter employs a modern gas chromatographic (GC) test procedure to analyze the distribution of fatty acid moieties that are attached to the three hydroxyl groups of the glycerin backbone if the sample is a fat or fixed oil. Fatty Acid Composition yields more detailed and reliable information when compared to these oil and fat structure index tests and thus has improved the identity determination of fats and fixed oils. Because Fatty Acid Composition can determine the percentages of each fatty acid group, structure indices, such as Iodine Value and Saponification Value, can be calculated or estimated based on the Fatty Acid Composition profile (15–17). However, Fatty Acid Composition is subject to considerable variation and presents challenges, the details of which are discussed in a later section.

Through the 2005 and 2006 revisions (12,13), the test for Acid Value was revised to include another titrant, to provide a calculation formula, and to add an additional test procedure allowing use of a different solvent mixture. The 2008 revision (11) replaced all the descriptive texts used in the calculations under the test sections with the appropriate calculation formula. Additionally, three new test sections were proposed: Omega-3 Fatty Acids Determination and Profile, Trace Metals, and Sterol Composition. These methods were introduced using a modern instrumental analysis approach. These additions enhanced the quality of general chapter <401> by providing compendial users further analytical methods that help to better characterize and evaluate fats, fixed oils, and related substances and that ensure purity of fixed oils and absence of adulteration.


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