BRIEFING
〈319〉 Nuclear Magnetic Resonance Spectroscopy Block Length Determination for Lactide–Glycolide Polymers. On the basis of USP's validated methods of analysis, a new chapter is being proposed by the Excipient Chapters Expert Committee (EXCC EC).
Lactide–glycolide and lactic acid–glycolic acid polymers (PLGs and PLGAs) are used extensively as excipients in complex extended-release drug products and medical devices. However, given the characterization and testing complexities of PLGs and PLGAs and a lack of standardized methods, their use in formulations and regulatory evaluation of the drug products containing these polymers remain challenging. USP continues to seek solutions and provide both compendial standards and emerging solutions for PLGs and PLGAs. USP’s compendial standards include Stimuli articles, monographs, and general chapters.
USP published two stand-alone general chapters (GCs), Nuclear Magnetic Resonance Spectroscopy Number-Average Molecular Weight Determination for Lactide-Glycolide Polymers with Ester End Groups 〈315〉 and Size Exclusion Chromatography Molecular Weight and Polydispersity Determination for Lactide-Glycolide Polymers Using Universal Calibration 〈316〉, to support stakeholders in applying advanced analytical methods to improve the characterization and quality of PLGs, prior to the incorporation of these methods into related official monographs. According to General Notices, 3.10 Applicability of Standards, “'Applicable general chapters' means general chapters numbered below 1000 or above 2000 that are made applicable to an article through reference in the General Notices, a monograph, or another applicable GC numbered below 1000". As such, the methods in these two GCs are not applicable to any USP–NF monographs. Block length is a critical quality and material attribute for PLGs and PLGAs. It describes monomer sequence distribution along the polymer chain, which significantly influences the polymer’s degradation profile. Stakeholders have requested a standardized method of block length determination to help better characterize these polymers.
Using this same stand-alone GC iterative approach, USP is working on developing this test method chapter to introduce the block length determination method.
As part of USP's stakeholder engagement model, on October 31, 2025, USP published a general chapter prospectus, which outlined the background for developing the chapter.
The current scope of this proposed chapter only covers analysis of lactide–glycolide polymers that are ring-opening copolymers of lactide and glycolide. USP will consider adding methods for other PLGs and PLGAs in the future with supporting validation data.
This proposal contains the following method: Block Length Determination Using Carbon NMR for the lactide–glycolide polymer.
Stakeholders are encouraged to contact USP to discuss any additional methods for characterization of PLGs and PLGAs.
(EXCC: P. Zhang)
Case ID—SUB-2676