Table 1.

Physicochemical, biopharmaceutical and pharmacokinetic disposition properties to perform simulations in GastroPlus™ for ibuprofen.

Input Parameter	Value/Selection Dynamic Settings	Value/Selection Default Settings	Reference
Physicochemical Properties
Molecular weight (g/mol)	206.29	206.29	ADMET Predictor 9.0
pKa (acidic)	4.54	4.54	ADMET Predictor 9.0
Octanol/water partition coefficient (logP)	3.65	3.65	ADMET Predictor 9.0
Biopharmaceutics Properties
Human effective permeability (Peff) (× 10−4 cm/s)	4.1	4.1	[27]
Particle size radius (um)	62	62	In-house data
Dose volume (mL)	250	250	[13]
pH at reference solubility	6.2	6.2	[28]
Solubility at reference pH (mg/mL)	1.99	1.99	[28]
Solubility in Fasted state human gastric fluid (FaHGF) (mg/mL)—pH 1.46	0.0048	0.0048	[29]
Solubility in Fasted state human intestinal fluid (FaHIF) (duodenum) (mg/mL)—pH 3.74	0.0102	0.0102	[29]
Solubility in FaHIF (jejunum) (mg/mL)—pH 4.6	1.2	1.2	[30]
Distribution and Clearance
Pharmacokinetic model	Two-compartmental	Two-compartmental	[31]
Clearance (L/h)	4.05	4.05	[31]
K10 (1/h)	1.16	1.16	[31]
K12 (1/h)	4.55	4.55	[31]
K21 (1/h)	3.46	3.46	[31]
Advanced Compartmental and AbsorptionTransit model (ACAT™) Model Parameters
Gastric transit time (h)	2.04	0.25	[13]
Dynamic fluid volume model	Based on 100% of the volumes measured in human MRI study after drinking a glass of water (240 mL)	Default static values under the physiology tab ‘Human—Physiological—Fasted’	[26]
Dynamic pH model	Based on average pH values derived from gastric, duodenal and jejunal aspirated fluids after oral administration of 800 mg of ibuprofen	Default static values under the physiology tab ‘Human—Physiological—Fasted’	[13]