Realistic Prediction of Solid Pharmaceutical Oxidation Products by Using a Novel Forced Oxidation System

Ueyama, Eiji; Tamura, K; Mizukawa, Kousei; Kano, Kenji

doi:10.1002/jps.23889

Cited by 4 publications

(1 citation statement)

References 26 publications

(53 reference statements)

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“…7 Polysorbates are prone to degradation via oxidation, [8][9][10] and chemical 7,9,12 and enzymatic hydrolysis, 11,[13][14][15] which may impact protein oxidation and potency, and affect product quality and shelf-life. 2,16 In previous studies, oxidative impurities in polysorbates 17 were found to degrade proteins 9 and other molecules 18 using PS-80 in the formulation. Thus, there has been significant interest across the pharmaceutical industry to fully characterize polysorbates and their degradation mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Advancing Structure Characterization of PS-80 by Charge-Reduced Mass Spectrometry and Software-Assisted Composition Analysis

Yang

Bush²,

DeGraan-Weber³

et al. 2022

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Advancing Structure Characterization of PS-80 by Charge-Reduced Mass Spectrometry and Software-Assisted Composition Analysis

Yang

Bush²,

DeGraan-Weber³

et al. 2022

Journal of Pharmaceutical Sciences

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Accelerated Stability Assessment Program to Predict Long-term Stability of Drugs: Application to Ascorbic Acid and to a Cyclic Hexapeptide

et al. 2021

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Influence of Crystal Disorder on the Forced Oxidative Degradation of Vortioxetine HBr

Modhave,

Barrios,

Iyer

et al. 2023

AAPS PharmSciTech

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The present study investigates the impact of the solid-state disorder of vortioxetine hydrobromide (HBr) on oxidative degradation under accelerated conditions. A range of solid-state disorders was generated via cryogenic ball milling. The solid-state properties were evaluated by calorimetry, infrared-, and Raman spectroscopies. While salt disproportionation occurred upon milling, no chemical degradation occurred by milling. The amorphous fraction remained physically intact under ambient storage conditions. Subsequently, samples with representative disordered fractions were mixed with a solid oxidative stressor (PVP-H2O2 complex) and were compressed to compacts. The compacts were exposed to 40°C/75% RH for up to 6 h. The sample was periodically withdrawn and analyzed for the physical transformations and degradation. Two oxidative degradation products (DPs) were found to be formed, for which dissimilar relations to the degree of disorder and kinetics of formation were observed. The degradation rate of the major DP formation obtained by fitting the exponential model to the experimental data was found to increase up to a certain degree of disorder and decrease with a further increase in the disordered fraction. In contrast, the minor DP formation kinetics was found to increase monotonically with the increase in the disorder content. For the similar crystallinity level, the degradation trend (rate and extent) differed between the single-phase disorder generated by milling and physically mixed two-phase systems. Overall, the study demonstrates the importance of evaluating the physical and chemical (in)stabilities of the disordered solid state of a salt form of a drug substance, generated through mechano-activation. Graphical Abstract

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Realistic Prediction of Solid Pharmaceutical Oxidation Products by Using a Novel Forced Oxidation System

Cited by 4 publications

References 26 publications

Advancing Structure Characterization of PS-80 by Charge-Reduced Mass Spectrometry and Software-Assisted Composition Analysis

Advancing Structure Characterization of PS-80 by Charge-Reduced Mass Spectrometry and Software-Assisted Composition Analysis

Accelerated Stability Assessment Program to Predict Long-term Stability of Drugs: Application to Ascorbic Acid and to a Cyclic Hexapeptide

Influence of Crystal Disorder on the Forced Oxidative Degradation of Vortioxetine HBr

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