Nanocrystal formation for the dissolution enhancement of glimepiride was attempted\nby wet media milling. Different stabilizers were tested and the obtained nanosuspensions were\nsolidified by spray drying in presence of mannitol, and characterized regarding their redispersibility\nby dynamic light scattering, physicochemical properties by differential scanning calorimetry (DSC),\nFT-IR spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microcopy (SEM), as\nwell as dissolution rate. Lattice energy frameworks combined with topology analysis were used in\norder to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with\nnarrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603\nstabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals\nduring spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic\ntransformations during processing, and that the milling process induces changes in the hydrogen\nbonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed\nthe existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD\nanalysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the\nimportant influence of the stabilizer on the dissolution rate of the nanocrystals.
Loading....