PARTIAL AMORPHIZATION OF POORLY-SOLUBLE SIMVASTATIN USP USING MEDIA MILLING IN SYNERGISM WITH SPRAY-DRYING
Objective: The objective of the current study was to explore top down methods of size reduction like High speed homogenisation and media milling in synergism with spray-drying in amorphization and solubility enhancement of BCS Class II antilipidemic drug Simvastatin USP.
Methods: Spray-dried micronized Simvastatin USP was formulated by homogenisation and media milling of drug suspension in optimized stabilizer solution. Stabilizer combination, duration of homogenisation and ball milling and drug:stabilizer ratio were optimized. The obtained dispersion was transformed into solid powder using spray-drying. The obtained Spray-dried micronized Simvastatin USP was evaluated for visual morphology, Infrared spectroscopy, Differential Scanning Calorimetry, in vitro drug release studies, X-Ray diffractometry, Scanning Electron Microscopy, contact angle measurement, solubility studies, dispersibility studies and intrinsic dissolution rate testing.
Results: Spray-dried micronized Simvastatin USP was found to show amorphization of crystalline Simvastatin USP as confirmed by absence of drug peak in Differential scanning calorimetry and lowered signal intensity in X-Ray diffraction studies. Spray-dried micronized Simvastatin USP was found to show enhanced drug hydrophilicity and solubility as confirmed by lowering in contact angle and increase in solubility and ease of dispersibility observations. In vitro dissolution testing and intrinsic dissolution rate testing were found to show increase in drug release from 11% to 79% and 4 mg min -1 cm -2 to 17 mg min -1 cm -2 for drug and Spray-dried micronized Simvastatin USP respectively.
Conclusion: Media milling in synergism with spray-drying was found to be a prospective solubility enhancement technique for poorly-soluble Simvastatin USP.
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