Co-milling of -cyclodextrin with simvastatin: Solid state studies and dissolution profile

Simvastatin is a cholesterol-regulating drug of widespread use in the prevention of cardiovascular diseases associated with dyslipidaemia. Herein we report on the preparation of co-amorphous adducts of simvastatin with the solubilising agent beta-cyclodextrin by means of a solvent-free mechanochemical procedure and on the evaluation of their dissolution profiles. Production of co-milled adducts was carried out using a laboratory scale planetary ball mill. The resulting powders were characterised by X-ray powder diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. Dissolution of simvastatin from the co-milled powders into water was measured by ultra-violet/visible absorption spectroscopy (UV/Vis). Results show that co-amorphisation was obtained after 280 min of milling the two components, with formation of a solid that features a much more favourable dissolution profile and allows simvastatin concentration in aqueous solution to reach a value roughly to nine folds higher than the one obtained by dissolving the pure drug. In conclusion, co-grinding with beta-cyclodextrin is a simple and quick method to obtain simvastatin preparations with an improved dissolution profile.