title: Humidity-corrected Arrhenius equation: The reference condition approach.
abstract: Accelerated and stress stability data is often used to predict shelf life of pharmaceuticals. Temperature, combined with humidity accelerates chemical decomposition and the Arrhenius equation is used to extrapolate accelerated stability results to long-term stability. Statistical estimation of the humidity-corrected Arrhenius equation is not straightforward due to its non-linearity. A two stage nonlinear fitting approach is used in practice, followed by a prediction stage. We developed a single-stage statistical procedure, called the reference condition approach, which has better statistical properties (less collinearity, direct estimation of uncertainty, narrower prediction interval) and is significantly easier to use, compared to the existing approaches. Our statistical model was populated with data from a 35-day stress stability study on a laboratory batch of vitamin tablets and required mere 30 laboratory assay determinations. The stability prediction agreed well with the actual 24-month long term stability of the product. The approach has high potential to assist product formulation, specification setting and stability statements.
authors.affiliation: SDC Slovenia, Lek Pharmaceuticals d.d., Verovškova 57, SI-1529 Ljubljana, Slovenia. Electronic address: klemen.naversnik@sandoz.com.
authors.forename: Klemen
authors.initials: K
authors.lastname: Naveršnik
authors.affiliation: SDC Slovenia, Lek Pharmaceuticals d.d., Verovškova 57, SI-1529 Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Jurečič
mesh_terms: D000465:Algorithms; D004355:Drug Stability; D006813:Humidity; D013607:Tablets; D013696:Temperature; D014815:Vitamins
chemical_list: D013607:Tablets; D014815:Vitamins
keywords: Accelerated stability; Arrhenius equation; Chemical stability; Forced degradation; Kinetics; Mathematical model; Shelf-life