Abstract
The objective of the present study was to formulate and characterize the poorly soluble drug simvastatin in order to enhance the solubility and dissolution characteristics. Simvastatin is a Biopharmaceutical classification system (BCS) Class II drug having very less solubility and therefore low oral bioavailability (5%). In the present study, simvastatin nanosuspensions were prepared by homogenization technique by using poloxamer 188 and poloxamer 407 with different ratios. The Lyophilized nanosuspensions were characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (pXRD), scanning electron microscopy (SEM) and infra red spectroscopy (FTIR). The nanosuspension was evaluated for drug content, saturation solubility and in-vitro dissolution studies. The pXRD profile of nanosuspension suggests that transformation of crystalline drug into amorphous form. DSC studies revealed that there was no interaction between drug and carrier. The effect of particle size was found to be significant on the saturation solubility of the drug and in-vitro drug release studies showed significant increase in the dissolution rate of nanosuspensions as compared with pure drug. This study has shown that initial crystalline state is changed to amorphous form due to particle size reduction. Saturation solubility with poloxamer 188 and poloxamer 407 was found to be 317.7 µg/ml and 218 µg/ml respectively when compared with pure drug. The dissolution profile with poloxamer 188 was better than with poloxamer 407, with former releasing 99.14 % drug in 60 minutes. In conclusion the results indicated nanosuspension technique by using poloxamer successfully used for enhancing the solubility of simvastatin. nanosuspension with poloxamer 188 showed suitability, as a stabilizer in the formulation of nanosuspension.
