Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Area of Science:

• Solid-state chemistry
• Crystallography
• Materials science

Background:

• Sulfaguanidine (SGD) polymorphism was first reported 65 years ago.
• Understanding solid-state forms is crucial for drug development and manufacturing.
• Polymorphism, hydrates, and solvates significantly impact compound properties.

Purpose of the Study:

• To comprehensively re-evaluate the solid-state behavior of sulfaguanidine (SGD).
• To identify and characterize novel anhydrate, hydrate, and solvate forms.
• To elucidate the stability relationships and transformation pathways of SGD solid forms.

Main Methods:

• Powder X-ray diffraction (PXRD) for structure determination.
• Calorimetric measurements (DSC/TGA) for thermal stability assessment.
• Computational crystal structure prediction for anhydrates and hydrates.

Main Results:

• Confirmed five anhydrates (AH-I-V), two monohydrates (Hy1-I, Hy1-II), and nine solvates.
• Reported nine novel structures: two anhydrates and seven solvates.
• AH-II is thermodynamically stable at low/room temperatures; AH-I is stable at higher temperatures.
• Controlled desolvation successfully produced AH-I, AH-II, and AH-V.
• Crystal structure prediction accurately identified observed forms and proposed AH-IV models.

Conclusions:

• Sulfaguanidine exhibits a rich and complex solid-state landscape.
• The study provides a detailed understanding of SGD's polymorphism, hydrates, and solvates.
• Findings serve as a model for investigating complex solid-state systems and their transformations.