Preparation and powder X-ray diffraction study of tecovirimat hydrate solid forms.

Area of Science:

• Solid-state chemistry
• Crystallography
• Pharmaceutical sciences

Background:

• Tecovirimat is a crucial antiviral medication targeting orthopoxviruses.
• The solid-state properties of tecovirimat, particularly its hydrated forms, are not fully understood.
• Understanding different solid forms is essential for drug formulation and stability.

Purpose of the Study:

• To identify experimental conditions for the reproducible crystallization of tecovirimat's hydrated forms.
• To characterize the solid-state landscape of tecovirimat.
• To determine the single-crystal structures of specific tecovirimat hydrates.

Main Methods:

• Crystallization experiments were performed under various conditions.
• Powder X-ray diffraction (PXRD) was used to confirm phase purity via Rietveld refinement.
• Single-crystal X-ray diffraction was employed to determine and re-determine crystal structures.

Main Results:

• Reproducible crystallization of three hydrated forms (two monohydrates, I and III; one hemihydrate, V) was achieved.
• The single-crystal structures of tecovirimat monohydrate I and hemihydrate V were determined for the first time.
• The crystal structure of tecovirimat monohydrate III was re-determined at 293 K for direct comparison.

Conclusions:

• This study successfully characterized three hydrated forms of tecovirimat, expanding knowledge of its solid-state properties.
• The determination of novel crystal structures provides a foundation for future solid-state research and drug development.
• Consistent characterization of these forms is vital for the reliable manufacturing and therapeutic use of tecovirimat.