Preparation, Characterization and Pharmacokinetic Studies of Ternary Mixed Micelles for Oral Administration of Diclazuril

A ternary mixed micelle comprised of sodium deoxycholate, RH 40 and Tween 80 was developed to enhance the solubility of diclazuril in water and to improve pharmacokinetic properties of diclazuril for oral administration. The mixed micelles were prepared by film hydration method and optimized by orthogonal test. The mixed micelles powder was characterized by using TEM, XRD and DLS. And the comparison of the pharmacokinetic properties of diclazuril loaded ternary mixed micelles and commercial diclazuril solution was conducted in rabbits as well. Results showed that there was synergistic solubilization between two of sodium deoxycholate, RH 40 and Tween 80 on diclazuril in water. The dosage of diclazuril, sodium deoxycholate, RH 40, and Tween 80 are 5, 200, 150, and 100 mg, respectively. XRD showed that diclazuril existed in the mixed micelles as the amorphous state, and the solubility of diclazuril in ternary mixed micelles was 3921.70 +/- 9.21 mu g/mL, which is 38.85 times than that of diclazuril in water. The pharmacokinetics showed that the ternary mixed micelles can increase C-max, t(1/2 alpha), and AUC significantly compared to diclazuril solution, whereas decrease T-max, CL, and V significantly on the other hand.