Effect of Carriers on Solid Dispersions of Simvastatin (Sim): Physico-Chemical Characterizations and Dissolution Studies

[摘要] The aim of the present work was to improve the solubility and dissolution rate of simvastatin(SIM), a drug used for the treatment of hyperlipidemia. Two systems were used: soliddispersions with PEG 4000 and PEG 6000 prepared using the fusion method in various ratioof 1:1, 1:3, and 1:5 and inclusion complexes with HP-β-cyclodextrin obtained by kneadingmethod in a ratio of 1:1 with drug SIM. The formulations were characterized in liquid stateby phase solubility studies and in the solid state by differential scanning calorimetry, X-raypowder diffraction, and FTIR spectroscopy. The aqueous solubility of SIM was studied in thepresence of PEG 6000. The dissolution profiles of solid dispersions and inclusion complexeswere determined and compared with those of SIM alone and the physical mixture. Inclusioncomplex prepared with HP-β-cyclodextrin by kneading method showed highest dissolutionrate of SIM. Dissolution studies indicated that the dissolution rate were markedly increasedin these solid dispersions systems compared with those in physical mixtures and pure drugalone. The increase in dissolution rate strongly depended on the type, ratios of drug tocarriers and selection of the method of preparations of solid dispersions. The soliddispersions compound prepared in the ratio of 1:1 by the HP-β-cyclodextrin by kneadingmethod showed the higest improvement in wettability and dissolution rate of SIM due to theamorphous formed and approxamately 100% of drug dissolved within 60 min . So thisamorphous SDs could be useful for further formulation as a suitable competative dosageforms.

[学科分类] 药理学