Research On Dissolution In Vitro And Bioequivalence Of Anastrozole Tablets

OBJECTIVESAnastrozole (’Arimidex’) is a potent and selective third-generation non-steroidal aromatase inhibitors which is indicated for the treatment of advanced breast cancer in postmenopausal women. It should now be considered as an alternative first-line therapy to tamoxifen in postmenopausal women. What’s more, it is recognized that anastrozole is more effective and well tolerated than the tamoxifen. The present study was aimed to determine the dissolution rate and bioequivalence of anastrozole tablets. Which produced by the biotechnology co.ltd of Bei Jing and AstraZeneca biopharmaceutical company, respectively.1. Methods and Results1.1The dissolution behavior of Anastrozole TabletsThe dissolution behavior of Anastrozole Tablets were detemined according to the dissolution methods of FDA and the national drug standards about anastrozole. The small cup method was used and the dissolution medium was water.2ml of dissolution medium were took out in the time of5,10,15,20,30min and the concentration of anastrozole were determined by HPLC.The results showed that solution behavior of two anastrozole tablets were almost the same and the dissolution rate of anastrozole in both preparations could reach above85%in ten minutes.1.2The bioequivalence of Anastrozole TabletsThe design was double cycle cross and own control. Each healthy volunteers take the2mg of anastrozole tablets orally. The test began after fasting12h,5.0ml of vein blood were collected and plasma was isolated at0.33h、0.67h、1h、1.5h、2h、3h、4h、6h、8h、12h、24h、48h、72h、96h、120h before and after drug administration. The anastrozole concentration in plasma was determined by LC-MS-MS. The results showed that the Cmax of test tablets and control tablets were33.31±7.31and32.37±5.71μg·L-1. Tmax were1.53±1.02and1.72±1.64h; t1/2were44.26±10.10and44.51±9.80h; AUC0-120were1420.52±324.79and1365.49±244.60μg·h·L1; AUC0-∞were1707.07±508.03and1631.891361.07μg·h·L-1respectively. The relative bioavailability of anastrozole in the test tablets was104.7%±18.6%. The90%confidence interval for the AUCo→120, AUC0→∞and Cmax were94.2%-113.2%,93.5%-113.7%and95.1%-109.6%, respectively. According to the ANOVA, the Tmax values were not statistically different compared to the control(P>0.05).2. Conclusions:The dissolution behavior of anastrozole in test tablets and the control drug was resemblance. And the anastrozole in test tablets was bioequivalent to the control drug.