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 Injections <1>. In 2006, stakeholders indicated that the test procedure for Unsaponifiable Matter described in general chapter <1> in USP 28–NF 23 was unclear and created uncertainty with regard to reporting of results (3).

USP staff and EM2 EC concluded that the test criterion for Unsaponifiable Matter under Other Vehicles in Ingredients, Vehicles, and Added Substances in <1> was subjective and thus unsuitable for its intended purpose, but the EC acknowledged the importance of the test for Unsaponifiable Matter for injectable products because it measured impurities such as waxes, phospholipids, and proteinateous matter to which patients could be allergic.

In addition, the original Cottonseed Oil NF monograph did not provide quality specifications for use as an injection vehicle. As a result, the monograph required revision to reflect its use in an intramuscular injection product. The EC also considered additional specific tests and appropriate acceptance criteria for this specific grade of oil.

EM2 EC collaborated with the Parenteral Products—Industrial EC to revise the tests under Other Vehicles in Ingredients, Vehicles, and Added Substances in <1> by means of a proposed revision published in 2008 (18). A quantitative test procedure for Unsaponifiable Matter and a test for Acid Value replaced the previous test for Unsaponifiable Matter and the test for Free Fatty Acids. Thus quantitative specifications for Acid Value and Unsaponifiable Matter were introduced. Three additional tests and acceptance criteria also were introduced into <1>: Peroxide Value, Water, and Limit of Copper, Iron, Lead, and Nickel. All three tests are critical quality control measures for fixed oils used in parenteral drug formulations. Usually, specifications for Peroxide Value and Water proposed under the Other Vehicles in <1> are more stringent than those implemented in the oils used for oral and topical products. The atomic absorption spectroscopy tests for Limit of Copper, Iron, Lead, and Nickel, referred to as Trace Metals in general chapter <401> were preferable to the method of general chapter Heavy Metals <231>. The quantitative Trace Metals test satisfied the accuracy requirements for much lower specification limits for parenteral products. If the oil had not been subjected to hydrogenation or if a nickel catalyst had not been used in processing, a note was included in the test for nickel stating that the test for nickel was not required, thus preventing unnecessary testing.

For cottonseed oil and other vegetable oils that have parenteral applications in drug formulations, the updated quality specifications in the Other Vehicles section in general chapter <1> were introduced and referenced in the fixed oil monographs.

Monograph labeling. The monograph Labeling section may contain a labeling requirement to differentiate a specific grade or chemical composition of the excipient. If a highly purified fixed oil will be used in injectable dosage forms (i.e., qualified as a specific grade), this is indicated in the Labeling section. Additional quality specifications for the specific grade may be necessary and can be included in Other Requirements under the Additional Requirements section of the monograph.


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