Co-evaporation method is better than freeze drying method to improve dissolution efficiency of simvastatin inclusion complexes with β-cyclodextrin

Abstract

Simvastatin is included in the biopharmaceutics classification system (BCS) class II, which is insoluble in water, causing limited absorption. Therefore, it is necessary to improve the solubility, one of which is through the formation of inclusion complexes with β-cyclodextrins. This study aims to analyze the simvastatin inclusion complex's characteristics with β-cyclodextrin through co-evaporation and freeze-drying and its dissolution profile. The simvastatin and β- cyclodextrin inclusion complexes were designed with two methods of inclusion complex formation, namely the freeze-drying process with a ratio of 1: 1 M (formula 1) and 1: 2 M (formula 2) and the co-evaporation method with a ratio of 1: 1 M (formula 3) and 1: 2 M (formula 4). At the same time, the control used single simvastatin and a single β-cyclodextrin. The characteristics of the inclusion complex were analyzed using infrared spectroscopy, X-ray diffraction (XRD), thin-layer chromatography (TLC), and UV-Vis spectrophotometry, while the dissolution test was carried out using the USP I tool. The expected test results showed changes in the spectrum and intensity of infrared spectroscopy, changes in diffraction pattern and intensity in XRD, decreased retention factor in TLC and decreased intensity in UV-Vis spectrophotometry after formation of inclusion complexes compared to simvastatin single. The dissolution test results showed an increase in dissolution efficiency of more than 50% compared to single simvastatin in all formulas. Simvastatin dissolution improvement also increases with increasing ratio. Also, the co-evaporation method with a ratio of 1: 2 M gave the highest yield among other formulas (88.66%). In conclusion, the formation of inclusion complexes can increase the dissolution of simvastatin by the co-evaporation method. Therefore, further research is needed to develop and design the simvastatin oral dosage form.