Self nano-emulsifying simvastatin based tablets: design and in vitro/in vivo evaluation

Abstract

The aim of this work is to improve the oral bioavailability of poorly water soluble drug, simvastatin (SV) through combining the advantages of self-nanoemulsifying systems (SNEs) and tablets. Ternary phase diagram was constructed using Labrafil, Tween 80 and Transcutol, in order to evaluate self-nanoemulsification domain. The particle size distribution and zeta potential of the prepared systems were evaluated using Malvern Zetasizer. Liquisolid powders were prepared using Aeroperl^® as a coating material and Avicel^® or Starch 1500 as carrier materials, the powder flow properties were then evaluated. Compressed SV SNE based tablets were evaluated regarding their physical characteristics, in-vitro release properties as well as in-vivo pharmacokinetic evaluation in six healthy human volunteers using a validated LC/MS/MS method. The in-vitro release results revealed that the developed SNE based tablets improved the release of SV significantly, compared to commercially available SV tablets (Zocor^®). The optimal SV SNE tablet formulation was S3St10 (10% Labrafil, 60% Tween 80, and 30% Transcutol). The in-vivo evaluation of S3St10 revealed that rapid and enhanced absorption of SV could be obtained from the SNE based tablet, with a 1.5 fold increase in bioavailability than that obtained after administration of Zocor^®. Hence such an approach could be promising in improving the bioavailability of SV.

Keywords::

• Simvastatin
• liquisolid powder
• self-nanoemulsification
• in vivo study; LC/MS/MS