Light-Induced Degradation of Tamoxifen in Liquid Formulations: Multivariate Kinetic Profiling, Stabilization Strategies, and Estrogen Receptor Binding

TL;DR

This study examines how light affects tamoxifen in liquid forms, identifies degradation products, and explores ways to stabilize the drug while assessing their impact on estrogen receptor binding.

Contribution

The paper provides the first integrated multivariate kinetic and molecular docking analysis of tamoxifen's photodegradation in liquid formulations.

Findings

Four photoproducts of tamoxifen were identified and found to retain estrogen receptor binding ability.

Stabilization strategies like protective packaging and chemical additives were evaluated for effectiveness.

Photodegradation products may contribute to tamoxifen's antitumor activity despite degradation.

Abstract

Tamoxifen is the most prescribed drug for the treatment
of breast
cancer in premenopausal women and prevention of tumor recurrence.
The anticancer effect is attributed to its ability to modulate estrogen
receptor activity, with the drug’s metabolites being more effective
than the parent compound. Tamoxifen is sensitive to environmental
conditions, leading to the formation of degradation products that
may, however, retain biological activity. Herein, the photodegradation
of tamoxifen in oral formulations was studied by combining spectrophotometric
methodologies and multivariate analysis. The four photoproducts identified
have been studied. Stabilization strategies were explored, evaluating
both protective packaging precautions and the addition of chemical
stabilizers, such as ascorbic acid and quercetin. Molecular docking
simulations revealed that all four photoderivatives are capable of
binding to the estrogen receptor, suggesting that these compounds
may retain, or contribute to, the drug’s antitumor activity.
These findings not only underscore the importance of formulation and
storage conditions in preserving tamoxifen stability and therapeutic
efficacy but also provide the first integrated multivariate kinetic
and molecular docking analysis of its photodegradation in liquid formulations,
offering novel insights into both stability and residual pharmacological
activity.

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