Formation and Characterisation of Posaconazole Hydrate Form.

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Posaconazole is an active pharmaceutical ingredient (API) used in oral suspensions.
• The intended Form I of posaconazole converts to Form-S during formulation, potentially impacting bioavailability.

Purpose of the Study:

• To investigate the polymorphic conversion of posaconazole Form I to Form-S.
• To understand the role of water in this conversion and identify methods for producing pure Form-S.

Main Methods:

• Polymorphic conversion was induced by water interaction.
• Posaconazole Form I wettability was assessed.
• Pure Form-S was isolated using dispersion in water followed by sonication (≥10 min).
• Characterization of Form-S included X-ray powder diffraction (XRPD), Raman spectroscopy, ATR spectroscopy, TGA, and optical microscopy.

Main Results:

• Water interaction was identified as the cause of polymorphic conversion from Form I to Form-S.
• Poor wettability of Form I presented challenges in achieving complete wetting and pure Form-S production.
• A method involving dispersion in water and 10 minutes of sonication successfully isolated pure Form-S.
• Posaconazole Form-S was characterized as a hydrate containing three water molecules per API molecule.

Conclusions:

• The polymorphic conversion of posaconazole is water-mediated and affects bioavailability.
• Optimized dispersion and sonication techniques are crucial for obtaining pure posaconazole Form-S.
• Posaconazole Form-S is a stable hydrate form with implications for drug formulation and delivery.