Type of Posting: General Chapter Prospectus
Posting Date: 29–Oct–2021
Expert Committee: Excipients Test Methods (ETM)
Proposed New Title: <312> Molecular Weight Determination for Alginates.
Input Deadline: 28–Nov–2021
Suggested audience: Excipient manufacturers, users, and regulators
Estimated proposal PF: 48(6) [Nov.-Dec 2022]
Background and objectives: During the 2015-2020 Excipients Expert Committees (ECs) Science Strategy discussions, the excipient ECs identified advancing the understanding and control of excipient composition and variability during formulation development and manufacturing and testing of pharmaceutical excipients as a key strategy:
- The USP excipient program team unit (PUT) initiated many internal research lab projects for development and validation of methodologies using advanced technologies for compositional analysis of complex excipients, especially existing polymeric excipients that lack specific testing. These technologies include Gel Permeation Chromatograph (GPC)/Size Exclusion Chromatograph (SEC) and NMR.
- In the 2020-2025 revision cycle, the ETM EC is now proposing to introduce these analytical methods through a general chapter approach. Part of USP's mission is focused on strengthening the global supply of quality medicines. A major priority and a key strategy for the Excipients group is to be 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 and control of excipient composition and variability. This proposed chapter and its approach will help allow USP to continue its relevance in establishing evolving approaches for excipient standards. In addition, this chapter will help the excipient ECs explore and expand analytics to assist and improve characterization of copolymers containing alkyl methacrylate or alkyl acrylate that will help identify better methods for establishing quality specifications.
- There were no specific methods for molecular weight determination of Alginic Acid, Potassium Alginate, and Sodium Alginate in USP-NF. Recent update of the definition of each of Alginic Acid, Potassium Alginate and Sodium Alginate monographs indicates that the typical average molecular weight is in the range of 10,000 – 600,000 g/mol. Viscosity specification is usually utilized to differentiate the multiple grades of polymers. However, the information from Alginate manufacturers indicated that establishment of standardized viscosity test is quite challenging for this type of natural polymeric products. Relative viscosities highly depend on test conditions and viscometer type. Thus, a standardized methodology based on size exclusion chromatography (SEC) with refractive index detector to determine weight-average molecular weight, number-weight average molecular weight and polydispersity for alginate products was developed and validated.
This new general chapter will help users better characterize composition and variability of these excipients.
Description of scope and application: The scope of this chapter will include SEC methods for determination of average molecular weight and polydispersity for alginic acid, potassium alginate and sodium alginate.
The general chapter is intended to be applicable for molecular weight analysis in Alginates.
Preliminary outline:
- Introduction
- Procedure
- Solutions preparation (including standard and sample solutions)
- Instrumental system
- System suitability requirements
- Analysis
Anticipated activities: USP is requesting early input from stakeholders on this proposal of a new chapter General Chapter<312>Molecular Weight Determination for Alginates, which is planned to be published for comments in Pharmacopeial Forum.
Contact: Devendra Chavan, Ph.D. (+91-9820871960, devendravasant.c@usp.org)
CN-22-022-00