Preparation,characterization and evaluation of oral bioavailability of albendazole hydrochloride
Objective Albendazole(ABZ)hydrochloric acid(HC1)salt(ABZ-HC1)was prepared,and the solid state properties,dissolution behavior in vitro,stability and oral bioavailability of the salt were evaluated.Method Crystallized ABZ-HCl was prepared by solvent evaporation method,and the prepared ABZ-HCl was validated by 1H-NMR.Solid state properties were characterized by powder X-ray diffraction(PXRD),dynamic water adsorption(DVS),thermogravimetric analysis(TGA),and differential scanning calorimetry(DSC).Measured the apparent solubility and intrinsic dissolution rate(IDR)of drug salts to observe their solubility and dissolution rate under different pH conditions.We conducted stability studies on ABZ-HC1 under strong light irradiation(4500±500 lx),high humidity(92.5％±5％RH),high temperature conditions(50±2)℃,and accelerated test conditions(40 ℃,75％±5％RH).Evaluated the pharmacokinetic behavior differences of ABZ and ABZ-HC1(25 mg·kg1)in rats..Results The formation of ABZ-HC1 was confirmed by 1H-NMR.There was a significant difference in the PXRD spectra between ABZ and ABZ-HC1.The DVS experimental results showed that the water absorption of ABZ raw material was poor,with a water absorption rate of only 3.86％at 90％relative humidity(RH),and the adsorption and desorption curves basically overlapped.However, ABZ-HCl quickly absorbed water in the initial 0-20％ RH range, and then slowly increased in mass. When RH reached 90％, the water absorption rate was 37.65％. During the desorption process, the adsorption and desorption curves of ABZ-HC1 were inconsistent, and there was a lag phenomenon. The results of TGA and DSC experiments showed that both substances had no adsorbed water, and the melting point of ABZ-HC1 was lower than that of ABZ. The results of in vitro dissolution experiments showed that the apparent solubility and IDR of ABZ-HC1 were 11.8 and 10.3 times higher than those of ABZ, respectively. ABZ-HC1 exhibited good physical stability. The in vivo pharmacokinetic results showed that compared with the ig ABZ raw material, the AUC0-24h and Cmax of ABZ-HC1 were significantly increased, by 8.8 and 6.9 times, respectively. Conclusion The prepared ABZ-HC1 can improve the solubility and oral bioavailability of ABZ, and has good physical stability.
albendazolehydrochloridesolid state propertiessolubilitystabilityoral bioavailability
NETL
NSTL
万方数据
