simvastatin | Acta Medica Marisiensis

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.

Quality Enhancement by Inclusion Complex Formation of Simvastatin Tablets

Rédai Emőke¹, Sipos Emese¹, Pocsai Zs², Tőkés B³, Székely P⁴

1 Pharmaceutical Technology Department, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
2 Bioeel SRL, Tîrgu Mureș, Romania
3 Physical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
4 Pharmaceutical industry and management Department, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

DOI: 10.2478/amma-2013-0052

Introduction: Simvastatin is an inhibitor of hydroxy-methyl-glutaryl-coenzyme A reductase, used in the treatment of hypercholesterolemia. To enhance its bioavailability by inclusion complexation, as host molecule randommethyl-β-cyclodextrin had been used. After evaluating the complexes we chose the kneading product in 1:2 molar ratio for incorporation of 10 mg simvastatin tablets.
Materials and methods: We prepared homogenous mixtures of the inclusion complex and some excipients. The tablets were prepared by direct compression. The tablets were evaluated in regard to: weight uniformity, thickness, diameter, hardness, friability, disintegration and dissolution profile.
Results: Weights are in the range of 196–208 mg, diameter 6.83–6.86 mm, height 3.86–4.01 mm, hardness 78.3–113.1 N, friability 0.75–1.19 %, disintegration above 15 minutes. The dissolved amounts of simvastatin from the tablets are higher compared to the dissolution of pure simvastatin, but lower than the dissolution of the complex itself. Excipients, like disintegrants and lubricants greatly influence the dissolution properties of the tablets.
Conclusions: According to our results, tablets containing inclusion complex of simvastatin exhibit better solubility, according to the dissolved amount of simvastatin, than pure drug alone. Proper physical parameters of the tablets are obtained by application of 5 % Primellose.