Nasir M. Idkaidek^1,, Naji Najib², Isam Salem², Jamal Jilani³

Aim of the study is to establish physiologically-based in vitro in vivo correlation (IVIVC) of azithromycin, a biopharmaceutics classification system (BCS) class II drug (high permeability/ low solubility). In vitro dissolution was done using USP apparatus II in pH 6 phosphate buffer at 50 rpm. In vivo pharmacokinetic study was done on 28 healthy humans after IRB and Jordan FDA approvals. Plasma sampling was collected up to 72 hours. Non compartmental analysis was done using Kinetica program V 5. Physiologically based IVIVC was conducted using linear IVIVC module of SimCYP program V 13. Physiological parameter of effective intestinal permeability was optimized along with IVIVC calculations. IVIVC dissolution prediction matched in vivo profile with 1% and 7.7% prediction errors for AUC₇₂ and Cmax, indicating proper physiologically based IVIVC. This is in agreement with IVIVC expectation for class II drugs according to (BCS) when in vitro dissolution rate is similar to in vivo dissolution rate. This is important for drug formulators to predict in vivo bioavailability from in vitro dissolution, which can save time and money.

azithromycin, IVIVC, SimCYP, Intestinal Permeability