2021 FDA Science Forum
Solid State 13C NMR Analysis of Patiromer
- Authors:
- Center:
-
Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Purpose
VELTASSA (patiromer sorbitex calcium oral powder) is a drug product approved for the treatment of hyperkalemia. The active moiety of the drug product, patiromer, is a cross-linked polymer consisted of three monomers: 2-fluoro-2-propenoate (m), diethenylbenzene (n) and octa-1,7-diene (p). However, the composition information about the polymer was not fully disclosed in the reference listed drug (RLD) labeling (m : (n+p) = 0.91 : 0.09, the ratio/amount of n and p is not listed). To facilitate the development of generic patiromer, we conducted research to develop a convenient and effective analytical method to characterize the chemical structure of patiromer.
Methods
To characterize the chemical structure and quantify the relative amounts of each monomer in the patiromer polymer, we employed solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy. Carboxylate, aromatic and aliphatic groups were first identified, evaluated, and quantified using cross polarization (CP), magic angle spinning (MAS) and other 13C SSNMR techniques to provide structural information of the polymer. Then, seven lots of patiromer (VELTASSA, purchased from pharmacy) were compared to investigate lot-to-lot variations and changes that may occur during the shelf-life of the drug.
Results
Various 13C-SSNMR techniques were used to account for cross polarization dynamics and ensure that quantitative data were acquired. It was found that the average patiromer sample contained 90.9 ± 0.4% carboxylate group (m), 7.6 ± 0.3% aromatic group (n), and 1.5 ± 0.4% aliphatic group (p) (mean ± SD, N=7). The resulting values agree well with values reported in the drug labeling while providing previously unpublished data on the relative amounts of n- and p-block rather than the sum of these two monomers. Seven different patiromer lots were compared. Little to no differences were observed between lots; neither as a function of dosage strength or time to expiration.
Conclusion
Our research demonstrates that SSNMR is a valuable and practical tool for analyzing polymeric materials like patiromer. The patiromer structure can be determined by evaluating the monomer components in the polymer. The quantitative data obtained from this study agree well with literature values. Comparison of the composition showed little to no lot-to-lot variability.
