Physical and Chemical Study of Simvastatin Inclusion Complexes

Rédai Emőke¹, Tőkés B.², Kiss A.³, Sipos Emese¹, Ciurba Adriana¹, Todoran Nicoleta¹

1 Pharmaceutical Technology Department, Faculty of Pharmacy, University of Medicine and Pharmacy Tîrgu Mureș
2 Physical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy Tîrgu Mureș
3 Organic Chemistry Department, Institute of Chemistry, Faculty of Science and Technology, University of Debrecen

Background: Simvastatin is an inhibitor of hydroxy-methyl-glutaryl-coenzyme A reductase, used in the treatment of hypercholesterolemia.
Aim: To enhance his bioavailability through inclusion complexation, as host molecule hydroxypropyl-b-cyclodextrin had been used. The objective of this study is to present our results of the study of some simvastatin and hydroxypropil-b-cyclodextrin (HPbCD) inclusion complexes. We analyzed the products by phase solubility study, dissolution test and Fourier-transformed Infrared Spectroscopy (FT-IR).
Methods: Complexes were prepared by kneading molecular ratios of 1:1 and 1:2 and compared also with physical mixtures. Solubility studies were performed in the presence of various HPbCD concentrations and the stability constant was calculated. The inclusion complexation was evaluated by dissolution and Fourier transformed infrared spectroscopy.
Results: When compared with the pure drug, the dissolution of simvastatin is improved in the presence of b-cyclodextrin derivates, depending on the complex preparation method.
Conclusions: The solubility of simvastatin increases as a function of HPbCD concentration. FT-IR study suggests the presence of intermolecular hydrogen bonds between simvastatin and HPbCD in inclusion complex.