BRIEFING
NMR Spectroscopy for the Determination of Degree of Hydrolysis for Polyvinyl Alcohol and Vinyl Alcohol Homopolymer, and Monomer Ratio for Vinyl Alcohol and Vinyl Acetate Copolymer 〈320〉. A new chapter, based on validated methods of analysis, is being proposed by the Excipients Test Methods Expert Committee (ETM EC). This chapter is applicable for the determination of the degree of hydrolysis in polyvinyl alcohol and vinyl alcohol homopolymer and of the monomer ratio in vinyl alcohol vinyl acetate copolymer. Part of USP's mission is to strengthen the global supply of quality medicines. Excipient standards are a major priority for USP and a key strategy in becoming a definitive source of global quality standards, to become more flexible and iterative in creating excipient standards, to expand on current compendial approaches, and thereby advance the understanding of and manage excipient composition and variability. This proposed chapter and its approach will enable USP to continue its relevance in introducing evolving approaches for excipient standards, which helps address the needs of regulatory agencies, excipient users, and excipient manufacturers with the current deficiencies of the official Polyvinyl Alcohol monograph. Although the current monograph has the test for determination of degree of hydrolysis in Polyvinyl Alcohol, the test is based on classical titrimetry, which is labor-intensive, nonspecific and involves use of methanol.
As part of USP's stakeholder engagement model, on August 30, 2024, USP published a general chapter prospectus for 〈320〉, which outlined the background on developing this general chapter. In addition, to provide the background and clarity to USP stakeholders, the ETM EC is proposing the following. In the Excipient Nomenclature Guidelines, Polyvinyl Alcohol, Vinyl Alcohol Homopolymer, and Vinyl Alcohol and Vinyl Acetate Copolymer have been documented and discussed in 4.4 Nomenclature of Synthetic Polymers. The FDA Inactive Ingredients Database (IID) and GSRS databases include multiple UNII and CAS numbers for Polyvinyl Alcohol. These are based on the differences related to degree of hydrolysis and weight-average molecular weight of the said material. Determining degree of hydrolysis values for different types of materials using the procedure available in the USP Polyvinyl Alcohol monograph is a laborious, time-consuming, and not an environment friendly activity. Thus, a standardized methodology based on nuclear magnetic resonance (NMR) to determine degree of hydrolysis, for different types of Polyvinyl Alcohol materials, has been developed and validated. The method included in the proposed general chapter will not replace the existing procedure available in the currently official monograph for Polyvinyl Alcohol. However, it will give an option to end users to use an advanced and faster methodology to determine the degree of hydrolysis for various types of polyvinyl alcohol materials with high accuracy and precision. The method has been successfully validated for the required parameters. All of the parameters were well within the acceptance criteria defined for the said parameters. This new general chapter will help users better characterize composition and variability of these excipients. This chapter is intended to be applicable for the determination of degree of hydrolysis in polyvinyl alcohol, vinyl alcohol homopolymer, and momomer ratio in vinyl alcohol and vinyl acetate copolymer. Other similar materials may be added as future revisions to this chapter. The ETM EC has agreed on developing this chapter as a below 〈1000〉 general test procedure chapter with a similar approach of other USP general test chapters such as Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Ethoxylated Substances 〈469〉.
The methods in this general chapter are not part of any monograph specifications unless the chapter is referenced in the monograph according to General Notices, 3.10 Applicability of Standards. The goal of developing this chapter is to help the EC explore and expand analytics to assist and improve the methodology for determining the degree of hydrolysis in different types of polyvinyl alcohol.
(ETM: D. Chavan)
Case ID—SUB-1633