Copovidone

Type of Posting: Notice of Adoption of Harmonized Standard

Posting Date: 24-April-2020

Official Date: 01–May-2021

Expert Committee: Excipient Monographs 2

Coordinating Pharmacopeia: Japanese Pharmacopoeia

The revision to the harmonized standard for Copovidone has been approved by the Pharmacopeial Discussion Group (PDG) as described in its PDG sign-off cover sheet. Having reached Stage 4 (former Stage 6) of the PDG process, the Copovidone monograph has been formally approved by the Excipient Monographs 2 Expert Committee in accordance with the Rules and Procedures of the Council of Experts.

The changes from the current Copovidone monograph include:

  • In the beginning of the monograph, added the statement: “Portions of this monograph that are national USP text, and are not part of the harmonized text, are marked with symbols test symbol symbol to specify this fact.
  • Chemical information
    • Add another two chemical names for Copovidone according to the PDG sign-off document.
  • Definition
    • Modify according to the PDG sign-off document by changing from: “The nominal K-value of copovidone as stated in the labeling is NLT 90.0% and NMT 110.0%.” to: “It contains NLT 7.0% and NMT 8.0% of nitrogen (N: 14.01), and NLT 35.3% and NMT 42.0% of vinyl acetate (C4H6O2: 86.09), calculated on the dried basis.”
  • Identification A
    • Specify that the Sample needs to be dried prior to the test.
  • Assay
    • Change the Acceptance criteria for Procedure 1: Content of Copolymerized Vinyl Acetate from 35.3%–41.4% to 35.3%–42.0%.
  • Residue on Ignition
    • Specify the sample amount and format the text according to USP style.
  • Limit of Aldehydes
    • According to the PDG sign-off document, acetaldehyde ammonia trimer trihydrate, instead of acetaldehyde, is used for the Standard solution preparation. The acetaldehyde concentration in the Standard solution is calculated accordingly. Water is used as the reference when determining the UV absorbance. The cell with water for reaction is used for blank test. USP is adding a [NOTE], as a USP local text denoted by test symbol, to further explain the origination of the factor used in the equation.
  • Limit of Hydrazine
    • Change the Developing solvent system from acetonitrile and water (17:3) to methanol and water (2:1), so the RF value is changed from about 0.6–0.7 to about 0.3.
    • Other minor changes are made based on the PDG sign-off document and editorial changes according to USP style.
  • Limit of Monomers
    • Replace the current method that determines the limit of 2-pyrrolidone, 1-vinyl-2-pyrrolidone, and vinyl acetate with two different methods for monomer analysis as follows:
    • One method is for 1-vinyl-2-pyrrolidone and vinyl acetate.
      • Suitable columns are from GL Science Inc. (Guard column: Inertsil ODS–4, 4.0-mm × 33-mm, 5-µm packing L1; and Analytical column: Inertsil ODS–4, 4.0-mm × 25-cm, 5-µm packing L1.) The retention times for 1-vinyl-2-pyrrolidone and vinyl acetate are about 17 and 22 min, respectively.
    • The other method is for 2-pyrrolidone.
      • Suitable columns are from GL Science Inc. (Guard column: Inertsil ODS–3, 4.0-mm × 10-mm, 5-µm packing L1; and Analytical column: Inertsil ODS–3, 4.6-mm × 15-cm, 5-µm packing L1. The retention time for 2-pyrrolidone is about 7 min.
  • pH
    • Add this new test according to the PDG sign-off document.
  • Loss on Drying
    • Specify the sample amount and format the text according to USP style.
  • K-Value
    • Clarify that the Acceptance criteria is based on the nominal K-Value stated in the Labeling.
  • Added test symbol symbols for Identification B and Package and Storage tests, because they are either non-harmonized attributes or local requirements for Copovidone NF monograph.
  • Additionally, minor editorial changes have been made to update the monograph to current USP style.

The Copovidone monograph will be incorporated into and become official in USP–NF 2021, Issue 1 (formerly known as USP 44–NF 39), from May 1, 2021.

Should you have any questions about the Copovidone monograph, please contact Tong (Jenny) Liu (240-221-2072 or jyl@usp.org). For any questions about the PDG and its processes, please see the Pharmacopeial Harmonization Group or contact Richard Lew at (240-221-2060 or rll@usp.org).