A physiologically-based drug absorption modeling for orally disintegrating tablets.Eur J Pharm Biopharm. 2020 Jul; 152:1-9.EJ
The aim of this research was to simulate oral pharmacokinetic (PK) profiles of atorvastatin from orally disintegrating tablets (ODTs) dosed without water ingestion in fasted humans. The in vitro dissolution profiles of three different formulations of ODTs were evaluated with fasted state biorelevant media using a paddle dissolution apparatus, and the results were coupled with an in silico model to simulate the in vivo oral PK profiles of ODTs following administration to humans. Since the dissolution rates of the ODTs in the intestinal medium (FaSSIF-V2) were highly affected by pre-exposure of the tablets to the stomach medium (FaSSGF), the simulation model took account of the relationship between the gastric emptying time and the dissolution performance of the tablets in the small intestine. The ODTs were formulated with drug-containing pellets. After oral dosing of the ODTs without water ingestion, gastric emptying of the pellets was assumed to follow first order kinetics. Thus, rate constants ranging between 0.69 and 8.3 h-1 were applied in the PK simulations. The simulation model was built using Stella Professional® software. The results of the PK simulations suggest that the plasma concentration profiles of the ODTs can be described using the prediction model, but that different gastric emptying parameters for each ODT formulation are needed in humans.