Single‐Dose Pharmacokinetic Properties and Relative Bioavailability of Different Formulations of Posaconazole Oral Suspension in Healthy Volunteers

Abstract The rate and extent of absorption of drugs belonging to Biopharmaceutics Classification System class II are rate‐limited by dissolution and highly dependent on the performance of the formulated product. The purpose of the present study was to investigate the potential impact of a surfactant and the particle size of the active substance on the in vitro drug dissolution profiles and in vivo pharmacokinetics of the poorly soluble drug posaconazole. A comparative physicochemical evaluation was conducted, and 3 formulations of posaconazole oral suspension were tested in various dissolution media compared with the reference product. In addition, a comparative bioavailability study was conducted in healthy volunteers under high‐fat fed conditions. Bioequivalence was assessed based on plasma concentrations of the parent drug (posaconazole) measured by a validated high‐pressure liquid chromatography‐tandem mass spectrometry method. The 90% confidence intervals for C max and AUC 0‐72 least‐squares mean T/R ratios of all 3 posaconazole formulations were within the bioequivalence acceptance range of 80.00% to 125.00%. The study was useful in the formulation development process and demonstrated that neither surfactant type nor particle size of the active substance within the studied range affected the extent or rate of absorption of posaconazole under the tested fed conditions.