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

Recommendations and criteria for modernization

EM2 EC recommendations for fixed-oil monographs. Fixed-oil excipients are used in a large number of drug products and are essential to product safety and performance. Thus, the successful manufacture of a robust product requires the use of well-defined excipients and processes that together yield consistent product quality. Typically, excipients are manufactured and supplied to comply with compendial standards. USP−NF excipient monograph specifications are not designated to explicitly test for material functionality, except for co-processed excipients (19). A greater understanding of the chemical composition and the physical and chemical properties of excipients is necessary to set compendial specifications in USP−NF monographs. The specificity of identification methods and specificity, precision, and accuracy of assay methods help prevent intentional adulteration and ensure a quality excipient. Such understanding provides the basis for well-defined and well-characterized excipients so that additional testing for product functionality and performance consistency can be employed by end users to yield consistent product quality.

Based on a literature review, comparative analysis of compendial specifications for fixed-oil articles in NF 23, and studies of fixed oils using modern analytical technologies, USP staff and EM2 EC made the following recommendations to modernize fixed oil monographs:
  • Introduce identification tests that are specific for chemical composition. A fingerprint or chemical profile—not all components or constituents must be individually identified—should be considered. Where possible, test for a greater number of nonoverlapping attributes by introducing a greater number of relatively simpler tests. In best cases, these tests can be performed orthogonally. Introduce tests that are generic and can be applied to most (if not all) fixed oils.
  • Introduce an oil chemical composition specification specific for relative compositional constituents such as fatty acids.
  • Introduce tests that identify and quantify the ingredient itself (e.g., component triglycerides rather than a surrogate).
  • Introduce specifications to identify natural or deliberate transformation and stability.

These recommendations are discussed below.

Recommendations for test procedures. EXC EC proposes several criteria for test procedures for fixed-oil excipient monograph modernization:

  • Universality of application
  • Ease of adoption—uses existing equipment and methodology to the greatest extent possible
  • Simplicity of procedure—a greater number of individual simpler tests is preferable to a smaller number of tests whose methodology is more complex and challenging
  • Specificity—any test or combination of tests must be able to uniquely identify the fixed oil and exclude the presence of other oils
  • Sufficient specificity to differentiate between an authentic fixed oil and an oil adulterated with the same oil of inferior quality
  • Preferably identify as well as assay a fixed oil using one method.


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