Moisture-dependent crystallization of amorphous lamotrigine mesylate

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous forms of drugs can crystallize upon moisture exposure, impacting stability and efficacy.
• Understanding moisture sorption and crystallization is vital for pharmaceutical formulation development.

Purpose of the Study:

• To investigate moisture sorption isotherms of lamotrigine mesylate (LTG-MES) amorphous forms.
• To identify sensitive indicators of moisture-induced crystallization.
• To compare amorphous forms prepared by different methods and their co-formulation with mannitol.

Main Methods:

• Computer-controlled vacuum moisture balance for isotherm determination.
• Polarized light microscopy, differential scanning calorimetry, and X-ray powder diffraction for crystallization verification.
• Analysis of weight-versus-time profiles and desorption hysteresis.

Main Results:

• Moisture sorption and crystallization behavior of spray-dried and freeze-dried amorphous LTG-MES were nearly identical.
• Desorption hysteresis and weight-versus-time profiles indicated moisture-induced crystallization.
• As little as 2% amorphous content was detectable using normalized water loss.
• Cofreeze-drying with D-mannitol yielded amorphous LTG-MES and crystalline D-mannitol.

Conclusions:

• Moisture sorption isotherms are sensitive indicators of crystallization in LTG-MES.
• Time scale effects are critical for defining moisture levels that trigger crystallization from the amorphous state.
• Amorphous LTG-MES prepared by different methods exhibit similar moisture-related properties.