Rod shaped nanocrystals exhibit superior in vitro dissolution and in vivo bioavailability over spherical like nanocrystals: A case study of lovastatin

The objective of this study was to compare the in vitro and in vivo performance of rod shaped and spherical like nanocrystals for oral administration. Lovastatin (LOV) was chosen as the model drug and LOV rod shaped nanocrystals (LOV-RNs) and spherical like nanocrystals (LOV-SNs) were prepared by sono-precipitation and bead milling, respectively. The dry powders obtained following freeze-drying, were characterized by hydrodynamic diameter, polydispersity index, zeta potential, transmission electron microscope, scanning electron microscope, atomic force microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy, and in vitro dissolution test. The pharmacokinetic study was performed in beagle dogs. The results obtained showed that LOV-RNs and LOV-SNs had similar hydrodynamic diameters (500.6 +/- 21.0 nm versus 503.2 +/- 20.4 nm), and the same crystalline state. The dissolution test showed that LOV-RNs had a higher dissolution rate than LOV-SNs. The AUC(0_24h) values of LOV-RNs and LOV-SNs were higher than Junning (R) for both LOV (p<0.05 for LOV-RNs, and p>0.05 for LOV-SNs) and lovastatin acid (p>0.05). More importantly, the oral bioavailability of LOV-RNs was higher than LOV-SNs (p>0.05). The findings of this study show that the crystal shape has a significant effect on oral bioavailability. (C) 2015 Elsevier B.V. All rights reserved.