Table I.

Summary of Drug Specific Physicochemical Input Data and Particle Size Distribution Parameters for Drug Material in Formulations

Molecular weight	543.5
Ionization constant	Neutral (base pKa <2)
logD at pH 7.4	3.03
Human permeability (10–4 cm/s)	3.5 (high)
Solubility (mg/mL) in fasted state simulating intestinal fluid: pH = 6.5a	0.025
Particle size distribution parameters for used formulations	D10b [μm]	D50c [μm]	D90d [μm]
Finely milled material for formulation in study SAD	0.9	2.3	5.1
Finely milled material for formulation in study REL_BA1 and REL_BA2	1.1	3.7	12.2
Coarsely milled material for formulation in study REL_BA1	3.7	27	109

Scaled from Caco2 cells using method described in (18)

SAD single-ascending dose

^aComposition of media is described in (5). Clinical dosage forms (standard capsules) were equilibrated for 24 h at 37°C, and the supernatant was analyzed by HPLC after centrifugation and filtration through a PVDF filter (0.45 μM)

^b10%,of the volume of drug material was measured as below the given diameter

^c50% of the volume of drug material was measured as below the given diameter

^d90% of the volume of drug material was measured as below the given diameter