Title:Early Prediction of the Chemical Stability of Drug Substances and Drug
Products during the Development Phase
Volume: 1
Author(s): Trupti Tol, Swapnil Mhamunkar, Harshad Tawde and Gautam Samanta*
Affiliation:
- Department of Quality by Design, Cipla Ltd, Vikhroli (West), Mumbai 400083, India
Keywords:
Chemical stability, Arrhenius equation, Accelerated stability assessment program, Shelf-life prediction, Iso-conversion, Development phase.
Abstract:
Background:
Traditional approach to shelf-life prediction claims a substantial amount of product development time, leading to significant delays.
Objective:
The capability of the unconventional Accelerated Stability Assessment Program (ASAP) to decode chemical stability and expedite shelf-life
prediction is discussed in the manuscript.
Methods:
As per the ASAP approach, shelf-life limiting attributes for two APIs’ and a formulation were identified based on the isoconversion ratio.
Isoconversion times at varying accelerated conditions were obtained and the degradation kinetics were modeled using the humidity-modified
Arrhenius equation. R2 and Q2 values were derived to assure model predictability. Temperature and humidity sensitivity of the attributes were
determined from the activation energy; Ea, and humidity sensitivity factor, B, respectively. Degradation plots demonstrated the dynamics of
degradation with time. The predicted values were verified by the available real-time data.
Results:
The degradation rate was modeled for impurities that exhibited conversion substantiated by an isoconversion ratio between 0.25-2.0. The Ea and B
data provided valuable details regarding the sensitivity of the products. Predicted shelf-life of less than a year for the finished product instigated
redevelopment. In the case of the APIs’, the existing storage conditions were found unsuitable for shelf-life stability, and alternate conducive
conditions were identified.
Conclusion:
The study provided cognizance regarding the distinct degradation pattern of an API and its formulation and the contradictory storage requirement
for APIs’ of two different molecules. While the traditional approach claims 3-6 months to predict shelf-life, the ASAP approach provides the same
with enhanced accuracy in just 3-4 weeks.
