Preparation and crystallographic analysis of gliclazide polymorphs

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Gliclazide is a widely used antidiabetic drug.
• Limited research exists on gliclazide's solid-state properties, specifically its polymorphism.
• Polymorphism significantly impacts drug solubility, stability, and bioavailability.

Purpose of the Study:

• To investigate solvent-induced polymorphism of gliclazide.
• To characterize the different polymorphic forms and amorphous powder.
• To evaluate the impact of polymorphism on gliclazide's solubility.

Main Methods:

• Solvent-assisted crystallization to produce polymorphs and amorphous powder.
• Characterization using infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and single-crystal X-ray diffraction.
• Equilibrium solubility measurements in aqueous media.

Main Results:

• Three distinct polymorphs (Form-I, Form-II, Form-III) and an amorphous powder of gliclazide were successfully prepared.
• Form-I (triclinic, P-1) has an endothermic peak at 162.93°C and higher solubility (0.4825 mg/ml).
• Form-II (monoclinic, P21/a) and Form-III (monoclinic, P21/n) showed lower solubility (0.2341 mg/ml and 0.2581 mg/ml, respectively) and are considered more stable.

Conclusions:

• Solvent manipulation can yield diverse solid forms of gliclazide.
• Polymorphic form significantly influences gliclazide's solubility, with Form-I showing the highest solubility, comparable to the amorphous form.
• Forms II and III represent more stable, less soluble polymorphs, crucial for formulation development.