Preparation and characterization of solid dispersion of simvastatin

Abstract

Context: Simvastatin (SIM), a widely used drug for the treatment of hypercholesterolemia, is a crystalline substance and practically insoluble in water. Its low dissolution rate leads to a poor absorption, distribution, and target organ delivery because the bioavailability of drugs with low aqueous solubility is limited by their dissolution rates. Objective: The aim of this study was to prepare solid dispersions (SD) of SIM with inert carriers in an attempt to improve the release profile. Methods: In this work, SIM SD with polyethylene glycol (PEG 6000) or polyvinylpyrrolidone (PVP K15) in 1:1, 1:2, 1: 3, 1:4, and 1:5 ratios were prepared and their stability and dissolution properties were investigated. SD were characterized by differential scanning calorimetry and X-ray powder diffraction. Tablets containing SD SIM : PEG 6000 were developed and their dissolution profile evaluated. Results: Drug release from all SD was significantly improved when compared to their corresponding physical mixture or SIM alone. SD SIM:PVP showed drug degradation. The tablets gradually released SIM with a final quantity greater than 80% in 60 minutes. Conclusions: The preparation of SIM SD with PEG or PVP is a promising strategy to improve the bioavailability of the drug. SIM SD with PEG are more advantageous over the dispersions prepared with PVP because they do not show drug degradation during preparation.

Keywords:

• Dissolution
• PEG
• PVP
• simvastatin
• solid dispersion
• solubility
• tablets

Acknowledgments

The authors are grateful to FAPEMIG for the financial support and CNPq (Brazil) for the fellowship to Silva, T.D.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.