Developability assessment of clinical drug products with maximum absorbable doses

International Journal of Pharmaceutics
Xuan DingJan Van Gelder

Abstract

Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application. Three methods for calculating D(abs) were compared by assessing how well the methods predicted the absorption limit for a set of real clinical candidates. D(abs) was calculated for these clinical candidates by means of a simple equation and two computer simulation programs, GastroPlus and an program developed at Eli Lilly and Company. Results from single dose escalation studies in Phase I clinical trials were analyzed to identify the maximum absorbable doses for these compounds. Compared to the clinical results, the equation and both simulation programs provide conservative estimates of D(abs), but in general D(abs) from the computer simulations are more accurate, which may find obvious advantage for the simulations in developability assessment. Computer simulations also reveal...Continue Reading

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Citations

Feb 26, 2015·Journal of Pharmaceutical Sciences·Kiyohiko Sugano, Katsuhide Terada
Dec 9, 2014·Journal of Pharmaceutical Sciences·Elizabeth Kwong
Mar 19, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Erik SjögrenPeter Langguth
Jul 18, 2016·Drug Discovery Today·Martin K BaylissAnthony J Taylor
Dec 16, 2017·Molecular Pharmaceutics·Vikram J PansareDavid T Vodak
Aug 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Song GaoDong Liang
Oct 26, 2018·Advanced Drug Delivery Reviews·A BakD J Brayden
Dec 17, 2021·Molecular Pharmaceutics·Stephen D Stamatis, John P Rose

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