Accelerated shelf life modeling of appearance change in drug products using ASAPprime^®

Abstract

An accelerated stability model approach was demonstrated to accurately predict the long-term shelf life of example drug substances and drug products (indigo carmine tablets and L-ascorbic acid powder) where appearance changes were shelf life–limiting. The products were exposed outside of packaging to conditions from 50 to 90 °C and 0–80% relative humidity for up to one month to accelerate appearance changes. The appearance changes of stressed samples were quantitated using the CIELAB color scale (calculated ΔE*), where a visual assessment of appearance changes likely to be noticeable was used to assign a ΔE* specification limit. ASAPprime^® software was employed to create an isoconversion paradigm, modeled in packaging by the moisture-modified Arrhenius equation, that predicted the color changes of the products within the error bars of the model to nine months at 25 °C/60% RH, 30 °C/65% RH, and 40 °C/75% RH. Overall, these case studies indicate that the ASAPprime^® approach for accelerated stability studies are a fast, accurate approach to modeling appearance changes.

Keywords:

• Predictive stability
• ASAP
• color
• appearance stability
• excipient incompatibility

Acknowledgments

The authors acknowledge Jennifer Chu and Lili Chen, both of FreeThink Technologies, Inc., for their assistance in experimental design and tablet fabrication. The authors also acknowledge Connor Lucey of FreeThink Technologies, Inc., for his work in editing and preparing this paper for submission.

Disclosure statement

ASAPprime^® is a proprietary software package produced by FreeThink Technologies.