Preparation, characterization, stability and in vitro-in vivo evaluation of pellet-layered Simvastatin nanosuspensions.

The objective of the present study was to develop stable pellets-layered Simvastatin (SIM) nanosuspensions with improved dissolution and bioavailability. The nanosuspensions were prepared with 7% HPMC, antioxidant 0.03% butylated hydroxyanisole and 0.2% citric acid (m/v) by low temperature grinding. After that, SDS with SIM was in a ratio of 1:5 (m/m), was evenly dispersed in the nanosuspensions. Then, they were layered on the surface of sugar pellets. The mean particle size of the SIM nanosuspensions was 0.74 µm, and 80.6% of the particles was below 1 µm in size. The pellets could re-disperse into nanoparticle status in the dissolution medium. In 900 mL pH 7.0 phosphate solutions, the dissolution of the layered pellets was better than that of commercial tablets. Also, nearly 100% of the drug dissolved from the pellets within 5 min under sink conditions. During the stability studies, SIM pellets exhibited good physical and chemical stability. The relative bioavailability of SIM and Simvastatin β-hydroxy acid (SIMA) for nanosuspensions layered pellets compared with commercial tablets was 117% and 173%, respectively. The bioavailability of SIMA was improved significantly (p < 0.05), confirming the improvement of bioavailability. Thus, the present study demonstrates that the pellet-layered SIM nanosuspensions improved both the dissolution and bioavailability of SIM.