Polymorphism of benzylthiouracil, an active pharmaceutical ingredient against hyperthyroidism

Area of Science:

• Solid-state chemistry
• Crystallography
• Materials science

Background:

• Benzylthiouracil is an antithyroid drug used to treat hyperthyroidism.
• Understanding the solid-state properties of pharmaceuticals is crucial for drug formulation and stability.
• Dimorphism, the existence of a compound in two crystalline forms, can significantly impact drug performance.

Observation:

• The crystal structures of dimorphic benzylthiouracil were redetermined.
• Atom coordinates for the two independent molecules of form I were obtained for the first time.
• Calorimetric studies revealed a phase transition from form II to form I at 405.4 K with an enthalpy of 5.6 J g⁻¹.
• Form I melts at 496.8 K with an enthalpy of 152.6 J g⁻¹.

Findings:

• The dimorphism of benzylthiouracil demonstrates its conformational versatility.
• Crystallographic and thermal expansion studies indicated that form II is denser than form I.
• The II-I equilibrium curve in the pressure-temperature phase diagram has a positive slope.
• This behavior is enantiotropic, with both solid phases having stable regions.

Implications:

• Form II is the stable polymorph under ambient conditions.
• The enantiotropic nature of benzylthiouracil's dimorphism has implications for its storage and formulation.
• Understanding these solid-state properties can aid in the development of more effective hyperthyroidism treatments.