Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation

Abstract

Background: Simvastatin is classified as a Biopharmaceutics Classification System (BCS) Class-II compound with a poor aqueous solubility and an acceptable permeability through biomembranes. The strategy of increasing the in vitro dissolution has the potential to enhance the oral bioavailability when using nanosized crystalline drugs.

Objective: The aim of this article was to prepare simvastatin nanocrystals to enhance its dissolution rate and bioavailability by exploiting sonoprecipitation.

Methods: Injecting 0.50% (w/v) methanol solution of simvastatin into 0.20% (w/v) water solution of F68 under sonication amplitude of 400 W and processing temperature of 3°C.

Results: Simvastatin nanocrystal with average diameter of 360 ± 9 nm could be obtained. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) confirmed the decreased crystallinity of nanoparticles stabilized by F68. The results of in vitro study demonstrated that the saturation solubility and dissolution rate of simvastatin nanocrystals were enhanced by 1 fold and 4 fold respectively, compared with crude simvastatin and the dissolution rate improved with the decrease in particle size. The C_max and AUC_(0–24 h) values of simvastatin nanocrystal group were approximately 1.50-fold and 1.44-fold greater than that of simvastatin nanocrystal group, respectively. Additionally, the T_max of simvastatin nanocrystal group was 1.99 h, comparing to 2.88 h of reference group.

Conclusion: Sonoprecipitation method can produce small and uniform simvastatin nanocrystals with an improved saturation solubility, dissolution rate and oral bioavailability.

Keywords::

• Nanocrystal
• Simvastatin
• sonoprecipitation
• dissolution rate
• bioavailability
• anti-solvent precipitation
• stabilizer

Acknowledgements

This work was supported by the National Basic Research Program of China (973 Program, 2009CB930300) and ATS Engineer Inc. China providing the ATS AH110D homogenizer.

Declaration of interest

The authors report no conflict of interest. The authors alone will be responsible for the whole content and writing of this paper.