(M1230-09-58) Photo-Stability of Peptides Exposed to LED, Fluorescent or UV Light in Liquid and Solid Formulations

Purpose: The photo-stability of new drug candidates can impact the drug product quality, generating aggregates or degradation products, as well as chemical modifications in the drug substance. Although, the light dose requirements are specified in the current version of ICH Q1B, there is no differentiation between small molecules and macromolecules. Moreover, recent studies have demonstrated that commonly used excipients such as methionine and citric acid can be responsible for the light absorption and generation of reactive oxygen species (ROS) in the formulation, which finally degrade the active pharmaceutical ingredient.

Methods: In this study, we evaluated different light sources, including light emitting diodes (LED), fluorescent and UV light on the formation of ROS in liquid formulations containing commonly used excipients. The photo-stability of a model peptide methionine-enkaphelin (MEn) was compared under different light sources in liquid and solid formulations.

Results: The tablet formulations were prepared with MEn, sodium citrate in basic or acid form, and spiked iron chloride hexahydrate mixed with common excipients. The tablets were exposed to light at different doses. The degradation products were evaluated using LC-UV and DESI-MS. Liquid formulations were prepared in citrate buffer, and iron chloride and the degradation products were evaluated with LC-UV and LC-MS.

Conclusion: Overall, formation of hydrogen peroxide, organic peroxides, formaldehyde and hydroxyl radicals were inferred under different light sources. Improved photostability of liquid formulations was observed after exposure to LED light. MEn degradation was observed on the surface of the tablets and liquid formulations after exposure to light.