Development of posaconazole nanosuspension for bioavailability enhancement: Formulation optimization, in vitro characterization, and pharmacokinetic study

Posaconazole (PSZ), an anti-fungal drug, has broad-spectrum activity. But its action is limited due to the poor solubility of posaconazole. The objective of the present study was to formulate and optimize posaconazole nanosuspension using a wet milling process. Final product quality was assured by a Quality by Design (QbD) approach that evaluated the impact of critical material attributes (CMAs) and critical process parameters (CPPs) on the critical quality attributes (CQAs) of the nanocrystals. The impact of crucial factors of critical material attributes (concentration of surfactant, concentration of polymer, and amount of drug) and critical process parameters (milling time) on particle size, polydispersity index (PDI), and zeta potential was studied using two-level full factorial design. The optimized nanocrystals had a particle size of 395.7 nm with a PDI of 0.30. The optimized formulation was characterized by DSC, FTIR, XRD, and surface morphology using SEM. XRD and DSC confirmed that there is no change in the crystalline state of PSZ is observed. The saturation solubility and in vitro dissolution study were performed for pure posaconazole and posaconazole nanosuspension. When compared to pure posaconazole, the solubility and in vitro release of the nanocrystals increased with reduced particle size in both 0.1 N HCl and phosphate buffer pH 6.8. According to in vivo pharmacokinetic results, the Cmax and AUC for PSZ nanocrystals increased significantly compared to pure PSZ.