Formation and Characterisation of Posaconazole Hydrate Form

Posaconazole is an API added as Form I for the production of oral suspensions, but it is found as Form-S in the final formulation. In this study, it was found that this polymorphic conversion, which may affect the bioavailability, is due to an interaction with water. However, the relatively poor wettability of posaconazole Form I renders the complete wetting of its particles and production of pure Form-S challenging. Consequently, for its isolation, Form I should be dispersed in water followed by application of sonication for at least 10 min. Pure posaconazole Form-S was characterised using X-ray powder diffraction (XRPD), Raman spectroscopy, attenuated total reflection (ATR) spectroscopy, thermogravimetric analysis (TGA) and optical microscopy. From these techniques, posaconazole Form-S was characterised as a hydrate form, which includes three molecules of water per API molecule.

Automated summary

This study found that the polymorphic conversion of posaconazole from Form I to Form-S, which may affect bioavailability, is due to an interaction with water. However, the poor wettability of posaconazole Form I makes it challenging to completely wet the particles and produce pure Form-S. Therefore, for isolation, Form I should be dispersed in water and subjected to sonication for at least 10 minutes. Pure posaconazole Form-S was characterized as a hydrate form containing three water molecules per API molecule using X-ray powder diffraction (XRPD), Raman spectroscopy, attenuated total reflection (ATR) spectroscopy, thermogravimetric analysis (TGA), and optical microscopy.