Asymmetrical Flow Field Flow Fractionation for Molar Mass Characterization of Polyethylene Oxide in Abuse-Deterrent Formulations

Haiou Qu; William C Smith; Xin Feng; Jiang Wang; Julia Pinto; Xiaoming Xu; Patrick J Faustino

doi:10.1016/j.chroma.2023.464186

Asymmetrical Flow Field Flow Fractionation for Molar Mass Characterization of Polyethylene Oxide in Abuse-Deterrent Formulations

J Chromatogr A. 2023 Aug 30:1705:464186. doi: 10.1016/j.chroma.2023.464186. Epub 2023 Jun 29.

Authors

Haiou Qu¹, William C Smith², Xin Feng², Jiang Wang², Julia Pinto³, Xiaoming Xu², Patrick J Faustino⁴

Affiliations

¹ Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993. Electronic address: Haiou.Qu@fda.hhs.gov.
² Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
³ Division of New Drug Product II, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
⁴ Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993. Electronic address: Patrick.Faustino@fda.hhs.gov.

PMID: 37453175
DOI: 10.1016/j.chroma.2023.464186

Abstract

High molar mass polyethylene oxide (HM-PEO) is commonly used to enhance the mechanical strength of solid oral opioid drug products to deter abuse. Because the properties of PEO depend on molar mass distribution, accurately determining the molar mass distribution is a necessary part of understanding PEO's role in abuse-deterrent formulations (ADF). In this study, an asymmetrical flow field-flow fractionation (AF4) analytical procedure was developed to characterize PEO polymers with nominal molar masses of 1, 4 or 7 MDa as well as those from in-house prepared placebo ADF. The placebo ADF were manufactured using direct compress or hot-melt-extrusion methods, and subjected to physical manipulation, such as heating and grinding before measurement by AF4 were performed. The molar mass distribution characterized by AF4 revealed that PEO was sensitive to thermal stress, exhibiting decreased molar mass with increased heat exposure. The optimized AF4 method was deemed suitable for characterizing HM-PEO, offering adequate dynamic separation range for PEO with molar mass from 100 kDa to approximately 10 MDa.

Keywords: Asymmetrical flow field-flow fractionation; abuse deterrent formulation; high molar mass polyethylene oxide; molar mass distribution.

MeSH terms

Abuse-Deterrent Formulations*
Drug Compounding
Fractionation, Field Flow* / methods
Polyethylene Glycols
Tablets

Substances

Polyethylene Glycols
Abuse-Deterrent Formulations
Tablets