Preparation of andrographolide derivative ISA-loaded bile salt-phosphatidy-I choline-mixed micelles and pharmacokinetics evaluation in rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare ISA-loaded bile salt-phosphatidylcholine-mixed micelles (ISA-BS/PC-MM) and study the release characteristics in vitro and pharmacokinetics in rats. METHODS: ISA-BS/PC-MM were prepared by film dispersion method. The formulation was optimized by the central composite design-response surface method. The release behaviors in vitro of the micelles were studied by dialysis method and its pharmacokinetic characteristics were studied by intrastric administration in rats. RESULTS: The drug concentration, entrapment efficiency, drug loading and average diameter of the optimized ISA-BS/PC-MM were 0.87 mg · mL-1, 86.34%, 4.87% and 148.3 nm, respectively. The release characteristics of ISA-BS/PC-MM were well fitted with Rither-Pep-pas equation. The pharmacokinetic data of ISA and I-SA-BS/PC-MM were in accord with two-compartment model. Compared with the original drug, micelles increased the absorption rate constant, shortened tmax, prolonged the elimination half-life and MRT, reduced the volume of distribution and clearance rate, and increased AUC. CONCLUSION ISA-loaded bile salt-phosphatidy-lcholine-mixed micelles can increase drug solubility and enhance bioavailability.