Objective  To prepare nifedipine nanocrystals (NDP-NCs) and evaluate their in vivo pharmacokinetics in rats.

Methods  The NDP-NCs was prepared by medium grinding method, and the formulation and preparation technology of NDP-NCs were determined by single factor experiment. The microstructure of NDP-NCs and its solid powder was observed under scanning electron microscope. The particle size distribution and Zeta potential of NDP-NCs before and after spray drying were compared. The stability of the spray drying granules of NDP-NCS was investigated. The dissolution rates of the NDP raw material and NDP-NCs granules were compared. The in vivo pharmacokinetics of NDP suspension and NDP-NCs granules were evaluated after oral administration in rats.

Results  Using hydroxypropyl cellulose (HPC-SL) and sodium dodecyl sulfate (SDS) as stabilizers, the ratio of drug to stabilizer was 5  ∶  1, the size of grinding medium was 0.2 mm, the ratio of grinding medium to liquid volume was 1 ∶ 1, the grinding speed was 2 000 r/min, and the grinding time was 3 h. The NDP- NCs showed an irregular granular distribution, and the NDP-NCs granules were porous and spherical. The average particle size and polydispersity index had no change before and after spray drying. The NDP-NCs granules had good stability after 6 months under the condition of accelerated testing. The solubility of NDP-NCs in different pH media was obviously improved. The dissolution rate of NDP-NCs granules increased significantly, and the drug could dissolve more than 90% within 15 min. The oral bioavailability of NDP was significantly improved after it was prepared into nanocrystals.

Conclusion  In this study, the nifedipine is prepared into nanocrystals with reasonable formulation design and feasible preparation technology, which can significantly improve the oral bioavailability of nifedipine.

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