Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

“…These predicted values were used as inputs for a Gastroplus PCAT model of nebulized amiloride HCl, where the predictions agreed reasonably well with available PK data in terms of C max and time to maximum plasma concentration, as illustrated in Figure , especially for the case in which the absorption rate constant in the pulmonary region was reduced by 50% . However, the model did overpredict area under the time‐concentration curve from time 0 to time ∞ (AUC 0‐∞ ) because of its inability to capture the trough between the double peaks, where the double peaks are present because of competing absorption processes in the lung and the gastrointestinal tract . After the validation case with nebulized amiloride HCl, the model was used to predict PK profiles for the four DPI‐based formulations, where significant differences were observed …”

“…In addition to current work using a CFD‐DEM approach, several recent studies have used CFD with the more traditional Lagrangian approach for particle tracking to investigate DPI performance . The use of CFD with Lagrangian particle tracking for the investigation of DPI performance was also recently reviewed by Sommerfeld et al .…”

“…Only a few studies have used the Pulmonary Compartmental Absorption & Transit (PCAT) model in Gastroplus to model absorption from OIDPs . The effect of different carrier properties on systemic PK was investigated by Wu et al .…”

“…Although most studies have used empirical or simplified analytical models to predict lung deposition for lung PBPK modeling of pharmaceutical drugs, two have used CFD . A CFD model using a Lagrangian particle‐tracking method was used to predict emitted dose, MMAD, and FPF of four amiloride hydrochloride (HCi) formulations from an Aerosolizer device, where predicted values showed reasonable agreement with impactor‐based emitted dose data, although MMAD values were underpredicted .…”

“…Although most studies have used empirical or simplified analytical models to predict lung deposition for lung PBPK modeling of pharmaceutical drugs, two have used CFD . A CFD model using a Lagrangian particle‐tracking method was used to predict emitted dose, MMAD, and FPF of four amiloride hydrochloride (HCi) formulations from an Aerosolizer device, where predicted values showed reasonable agreement with impactor‐based emitted dose data, although MMAD values were underpredicted . These predicted values were used as inputs for a Gastroplus PCAT model of nebulized amiloride HCl, where the predictions agreed reasonably well with available PK data in terms of C max and time to maximum plasma concentration, as illustrated in Figure , especially for the case in which the absorption rate constant in the pulmonary region was reduced by 50% .…”