Preparation of sustained-release microspheres of nifedipine with micelle solubilization and its in vivo pharmacokinetic study / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare nifedipine-mPEG-g-Zein sustained-release microspheres, making use of the mechanism that hydrophilic mPEG-g-Zein can be self-assembled into micelles in the water to increase the solubility of the poorly water-soluble drug nifedipine, and to examine its in vitro and in vivo release behaviors. METHODS: The nifedipine-mPEG-g-Zein microspheres were prepared by the method of suspension interfacial crosslinking. Polyvinyl alcohol (PVA) was used as the capsule material. The particle size, drug-loading rate, encapsulation efficiency and the total in vitro drug release were examined. The plasma levels of nifedipine at different time points were determined by HPLC after oral administration of a single dose of the self-made microspheres (test formulation) and marketed tablets (reference formulation) to mice. The pharmacokinetics and relative bioavailability were analyzed. RESULTS: The average diameter of the microcapsules was 22 μm (in which the average particle size of nano-micelles was 200 nm), and the drug loading, encapsulation efficiency, and the total in vitro drug release were 15.16%, 85.8% and 93.8%. The relative bioavailability the microspheres to the tablets was 166%. CONCLUSION: The microspheres are round and the size distribution is uniform. Meanwhile, the in vitro release profile shows obvious sustained-release characteristics, and the relative bioavailability is increased.