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

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: solid dispersions with PEG 4000 and PEG 6000 prepared using the fusion method in various ratio of 1:1, 1:3, and 1:5 and inclusion complexes with HP-I²-cyclodextrin obtained by kneading method in a ratio of 1:1 with drug SIM. The formulations were characterized in liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FTIR spectroscopy. The aqueous solubility of SIM was studied in the presence of PEG 6000. The dissolution profiles of solid dispersions and inclusion complexes were determined and compared with those of SIM alone and the physical mixture. Inclusion complex prepared with HP-I²-cyclodextrin by kneading method showed highest dissolution rate of SIM. Dissolution studies indicated that the dissolution rate were markedly increased in these solid dispersions systems compared with those in physical mixtures and pure drug alone. The increase in dissolution rate strongly depended on the type, ratios of drug to carriers and selection of the method of preparations of solid dispersions. The solid dispersions compound prepared in the ratio of 1:1 by the HP-I²-cyclodextrin by kneading method showed the higest improvement in wettability and dissolution rate of SIM due to the amorphous formed and approxamately 100% of drug dissolved within 60 min . So this amorphous SDs could be useful for further formulation as a suitable competative dosage forms.