Preparation and characterization of nebivolol hydrochloride HP-β-CD inclusion complexes

ZHOU Yun; FU Xu-dong; BI Shi-tao

Abstract：Objective: To prepare nebivolol hydrochloride hydroxypropyl-β-cyclodextrin (HP-β-CD )inclusion complexes, and investigate the improvement effect of HP-β-CD on the dissolution of nebivolol hydrochloride. Methods: The inclusion complex was prepared by solution-mixing and freeze-drying method and optimized by L9(34)orthogonal design with mole ratio of nebivolol hydrochloride to HP-β-CD, inclusion temperature, inclusion time and ethanol concentration as factors, using inclusion rate as evaluation index. Phase solubility method, infrared spectrophotometry (IR)and X-ray diffraction (XRD)were conducted to verify the inclusion complexes. The inclusion rate and dissolution were determined by HPLC. Results: The optimum inclusion process was as follows: the mole ratio of nebivolol hydrochloride to HP-β-CD was 1∶1, inclusion temperature was 40℃, inclusion time was 4 h, and ethanol concentration was 80％ (V/V). The verifying experiment indicated that nebivolol hydrochloride and HP-βCD formed inclusion complexes, and phase solubility curve indicated ALtype. The analysis showed significant difference between the inclusion complexes and physical mixture. Under the optimal process, the inclusion rate of inclusion complexes were (73. 69 ± 0. 10)％ as measured by HPLC. The solubility of the inclusion complexes were 3. 18 and 11. 10 times higher than that of nebivolol hydrochloride in purified water and pH 6. 8 phosphate buffer. Conclusion: Solution-mixing and freeze-drying method is reasonable and practicable to prepare inclusion complexes and it can improve the solubility of nebivolol hydrochloride.