PURPOSE: To propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life. MATERIALS AND METHODS: The concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations. RESULTS: Examples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions. CONCLUSIONS: The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.
PURPOSE: To propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life. MATERIALS AND METHODS: The concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations. RESULTS: Examples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions. CONCLUSIONS: The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.
Authors: Karen M Alsante; Peter Boutros; Michel A Couturier; Robert C Friedmann; Jeffrey W Harwood; George J Horan; Andrew J Jensen; Qicai Liu; Linda L Lohr; Ronald Morris; Jeffrey W Raggon; George L Reid; Dinos P Santafianos; Thomas R Sharp; John L Tucker; Glenn E Wilcox Journal: J Pharm Sci Date: 2004-09 Impact factor: 3.534
Authors: Karen M Alsante; Kim Huynh-Ba; Steven W Baertschi; Robert A Reed; Margaret S Landis; Mark H Kleinman; Christopher Foti; Venkatramana M Rao; Paul Meers; Andreas Abend; Daniel W Reynolds; Biren K Joshi Journal: AAPS PharmSciTech Date: 2013-11-27 Impact factor: 3.246
Authors: Bertrand Roduit; Charles Albert Luyet; Marco Hartmann; Patrick Folly; Alexandre Sarbach; Alain Dejeaifve; Rowan Dobson; Nicolas Schroeter; Olivier Vorlet; Michal Dabros; Richard Baltensperger Journal: Molecules Date: 2019-06-13 Impact factor: 4.411