High molecular weight (HMW) polyethylene oxide (PEO) has been widely used in solid oral opioid formulations to impart abuse-deterrent (AD) properties. Specifically, the molecular weight (MW) of PEO is one of the critical quality attributes that could impact the properties of the PEO polymer as well as the performance of the product. For example, it is known that HMW-PEO may degrade under oxidative stress such as during the manufacturing or manipulation (e.g. heat). As such, the PEO MW distribution may change, which could lead to undesired changes in solution viscosity (an important measure for injection abuse potential). Accurate determination of the MW distribution of PEO is therefore vital to understand its role in abuse-deterrent formulations. Asymmetric flow field flow fractionation (AF4) is a high-resolution separation technique that has been demonstrated to be a more effective method over size-exclusion chromatography in characterizing high molecular weight polymers. However, there is currently no reports in the scientific literature that documents the use of AF4 techniques for HMW PEO analysis. The aim of this study is to develop a method based on AF4 to determine the MW distribution of PEO up to 8 million Da. PEO standards (up to 1.3 million Da) and polystyrene nanoparticles were used for method development. Experimental factors, including mobile phase composition and concentration, focus flow, focus/injection duration and cross flow profile, were optimized. Online detectors including MALS, DLS and RI were coupled to the AF4 to acquire information on the MW, radius of gyration and hydrodynamic size of the polymer. Several commercial PEO products with nominal molecular weight from 300 kDa to 8000 kDa were stored at elevated temperature to induce thermal degradation. Decrease in the average molecular weight and increase of small PEO segments were observed. The results provided an evaluation of suitability of using AF4 technique to study the stability of HMW PEO under different manufacturing conditions.

Characterization of high-molecular weight polyethylene oxide in abuse-deterrent opioid formulations using asymmetric flow filed flow fractionation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.