Applying the methodology of Design of Experiments to stability studies: a Partial Least Squares approach for evaluation of drug stability

Abstract

The aim of the present research is to show that the methodology of Design of Experiments can be applied to stability data evaluation, as they can be seen as multi-factor and multi-level experimental designs. Linear regression analysis is usually an approach for analyzing stability data, but multivariate statistical methods could also be used to assess drug stability during the development phase. Data from a stability study for a pharmaceutical product with hydrochlorothiazide (HCTZ) as an unstable drug substance was used as a case example in this paper. The design space of the stability study was modeled using Umetrics MODDE 10.1 software. We showed that a Partial Least Squares model could be used for a multi-dimensional presentation of all data generated in a stability study and for determination of the relationship among factors that influence drug stability. It might also be used for stability predictions and potentially for the optimization of the extent of stability testing needed to determine shelf life and storage conditions, which would be time and cost-effective for the pharmaceutical industry.

Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances

“…Furthermore, because AQbD for analytical methods is an extension of QbD for pharmaceutical processes, it may also be used for other applications, such as optimization of sample preparation ,, or evaluation of stability studies . In the case of tablet sample preparation, examples of studied factors are the time of sonication/shaking/stirring, the temperature of the ultrasonic bath, the solvent composition, filtration, etc.…”

Stability, biofunctional, and antimicrobial characteristics of cannabidiol isolate for the design of topical formulations

“…6 CBD is reported to be an unstable ingredient when exposed to acidic pH, temperature, light, and air. [13][14][15][16] Hence, it is imperative to define the environmental conditions to be used while formulating CBD-based products. Stability studies of the ingredient are essential prior to formulation development to guarantee its proper handling and formulation.…”