Abstract
Nanocrystal formation for the dissolution enhancement of glimepiride was attempted by wet media milling. Different stabilizers were tested and the obtained nanosuspensions were solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility by dynamic light scattering, physicochemical properties by differential scanning calorimetry (DSC), FT-IR spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microcopy (SEM), as well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603 stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic transformations during processing, and that the milling process induces changes in the hydrogen bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the important influence of the stabilizer on the dissolution rate of the nanocrystals.
Highlights
The oral route of administration is considered as the first choice for drug administration due to its convenience, non-invasiveness, good patient compliance and the lowest cost of therapy
Different stabilizers were tested and the obtained nanosuspensions were solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility by dynamic light scattering, physicochemical properties by differential scanning calorimetry (DSC), FT-IR spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microcopy (SEM), as well as dissolution rate
Lattice energy framework and topology analysis revealed the existence of a possible slip plane on the (101) surface, which was experimentally verified by Powder X-ray Diffraction Analysis (PXRD) analysis
Summary
The oral route of administration is considered as the first choice for drug administration due to its convenience, non-invasiveness, good patient compliance and the lowest cost of therapy. Numerous approaches have been applied to overcome problems in oral delivery of poorly soluble drugs, such as salt formation [2], formulation of solid dispersions [3] and lipid based drug delivery systems [4], inclusion complexation with cyclodextrins [5,6], particle size reduction [7], etc. In the present study, glimepiride, a third-generation sulfonylurea oral hypoglycemic agent used for the treatment of patients with type II non-insulin-dependent diabetes mellitus [14], was selected as a model drug for nano-comminution Since it exhibits very low solubility at acidic and neutral pH (
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