Crystal morphologies and polymorphs in tolbutamide microcrystalline powder

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Crystallography

Background:

• Crystal habit significantly impacts drug tableting behavior.
• Pharmaceutical companies require accurate crystal morphology prediction for active pharmaceutical ingredients (APIs).
• Tolbutamide, an anti-diabetic drug, exhibits complex polymorphism affecting its properties.

Purpose of the Study:

• To predict the crystal morphology of tolbutamide using computational and experimental methods.
• To analyze the structural properties and polymorphism of tolbutamide.
• To correlate molecular structure with observed crystal habit.

Main Methods:

• Quantitative phase analysis via X-ray powder diffraction.
• Molecular mechanics calculations.
• Optical microscopy (OM) for morphology observation.
• Comparison of predicted and observed crystal habits.

Main Results:

• Identified the proportion of different crystallographic structures in commercial tolbutamide powder.
• Predicted crystal morphologies based on molecular mechanics calculations.
• Compared predicted morphologies with experimental observations from OM.
• Discussed structure-habit relationships and the influence of crystallization solvents.

Conclusions:

• Bridged the gap between molecular structure and crystal habit for tolbutamide.
• Provided insights into optimizing industrial crystallization processes for APIs.
• Highlighted the importance of understanding polymorphism for drug development.