Modified crystal habits of glimepiride to improve manufacturing processability

Abstract

Form I of glimepiride (GMP) with irregular crystal habit was chosen to develop an appropriate crystal habit to improve its dissolution and other material attributes such as cohesiveness, flow behavior, plastic deformation, yield pressure, compressibility, compactibility, and tensile strength. Modified habits generated were hexagonal (GMP-A), rhombohedral (GMP-B), and tabular (GMP-C). Scanning electron microscopy (SEM) and generated morphology confirmed the shape of the habits. Solid-state properties were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA), which confirmed that no polymorphic transition occurred. Flow characterization, Kawakita, and Heckel analysis, studies on tensile strength, compressibility, compactibility, and dissolution proved that modified habits have better flow, less cohesive nature, linear plastic deformation, low yield pressure, better compressibility, compactibility, tensile strength, and dissolution profile over irregular crystal habit (p < 0.05). Amongst the obtained habits, GMP-C performs better in all aspects over the rest of the habits and hence will be a good choice for further formulation development.