Physical barrier type abuse-deterrent formulations: monitoring sintering-induced microstructural changes in polyethylene oxide placebo tablets by near infrared spectroscopy (NIRS)

Abstract

Objective: The monitoring and evaluation of sintering-induced tablet strength of a polyethylene oxide (PEO) based placebo tables was accomplished using infrared spectroscopy (NIRS).

Significance: Evaluation of high molecular weight PEO-based tablet matrices for abuse deterrent formulation applications is an analytical challenge. NIRS is one tool that can provide physical and chemical evaluation of this polymer and tablet system. In addition, the use of NIRS as a process analytical tool (PAT) to monitor oven sintering of pharmaceutical tablets has not been recorded in the literature. The multiplicative scattering correction (MSC) algorithm was also successfully applied as a new and fast way to calculate NIRS spectral slopes and intercepts to build models against tablet tensile strength with respect to sinter time.

Methods: Both spectral slope regression (SSR) and spectral intercept regression (SIR) models were compared to commonly used partial least squares analysis (PLS) to evaluate placebo PEO based pharmaceutical tablets comprised of PEO at 70, 50, 30% w/w that were compressed at two solid fraction (SF) levels.

Results: All three regression techniques, PLS, SSR, SIR, were evaluated for robustness and reliability and physical relevancy to the system studied. The methods were ranked in utility with SSR being the best method followed by SIR then PLS.

Conclusions: The MSC algorithm was presented to quickly calculate spectral slopes and intercepts for use in SSR and SIR analysis. SSR models were successfully applied and assessed as the optimal modeling technique to monitor sintering of PEO-based matrix tablets.

Keywords:

• Abuse deterrent formulations
• polyethylene oxide
• process analytical technology
• sintering

Acknowledgements

The authors would like to acknowledge the National Institute for Pharmaceutical Technology and Education (NIPTE) and the U.S. Food and Drug Administration (FDA) for providing funds for this research. The content of this paper was part of the graduate thesis dissertation submitted by Heather J. Boyce to the faculty of the School of Pharmacy, University of Maryland, Baltimore in partial fulfillment of the requirements for the doctorate degree in pharmaceutical sciences – 2017.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was funded by the FDA contract to NIPTE Grant # HHSF223201301189P.