Developing suspension formulations with different production techniques of posaconazole and evaluation of in vitro performances

Posaconazole is a BCS Class II molecule used for treating systemic fungal infections, preferred in the treatment due to its superiority over other antifungals. The solubility of posaconazole is the rate-limiting step in oral bioavailability and poses challenges in optimizing suspension formulations. In this study, we aimed to compare two different techniques for the milling, which is one of the critical processes in the production of the suspension formulation of posaconazole, to evaluate the effect of the process parameters. Posaconazole suspension formulations were aimed to have a similar in vitro dissolution rate to the reference product, and particle size distribution and viscosity were determined as critical quality properties. The formulation components that affect these two critical properties are surfactant and suspending agent. First, the amount of these to be used was determined, then the effect of the milling process was evaluated. A high-shear homogenizer (Ultraturrax device) and media (bead) mill (Dyno Mill devices) were used for the milling process. The dissolution rate analyzes of the prepared formulations were compared with the reference product (Noxafil Oral Suspension) and the performance of the products was evaluated with the f2 similarity factor. In this study, we found that despite using formulations with the same components in the same amount and with the same production steps for suspensions, different in vitro performances were obtained when devices with different milling principles were used. We also found that the milling process has significant effects on the critical quality properties and homogenization of the suspensions.