Integrating Drug- and Formulation-Related Properties With Gastrointestinal Tract Variability Using a Product-Specific Particle Size Approach: Case Example Ibuprofen.
In the present study, an in vitro-in vivo extrapolation of dissolution integrated to a physiologically based pharmacokinetics modeling approach, considering a product-specific particle size distribution and a self-buffering effect of the drug, is introduced and appears to be a promising translational modeling strategy to support drug product development, manufacturing changes and setting clinically relevant specifications for immediate release formulations containing ibuprofen and other weak acids with similar properties.
['Cristofoletti|Rodrigo|R|', 'Hens|Bart|B|', 'Patel|Nikunjkumar|N|', 'Esteban|Valvanera Vozmediano|VV|', 'Schmidt|Stephan|S|', 'Dressman|Jennifer|J|']
D000284:Administration, Oral D000328:Adult D002626:Chemistry, Pharmaceutical D000076722:Drug Development D065546:Drug Liberation D041981:Gastrointestinal Tract D006801:Humans D007052:Ibuprofen D008954:Models, Biological D010316:Particle Size D012995:Solubility
particle size dissolution absorption in vitro-in vivo (IVIVC) correlation(s) mechanistic modeling physiologically based pharmacokinetic (PBPK) modeling