The Development Of The Targeted Therapy Gefitinib Dispersible Tablet For Lung Cancer

Objective Gefitinib (AstraZeneca and Teva), is a molecular target drug used for lungcancer therapy by the function to inhibit signaling through the epidermal growth factorreceptor(EGFR) tyrosine kinase in target cells. At present, The Gefitinib used in the marketis only the normal tablets. However, low dissolvability and low bioavailability of theGefitinib become the most significant problem during its application. In this study,dispersible tablet was chosen as the dosage form to improve the bioavailability.Method For the preparation part, An initial formulation was established by usingcondition of the surface, dispersal homogeneity and dissolution as parameters to selectproper filler, disintegrating agent and acidifying agent, etc. Then the formulation wasoptimized by central composite design-response surface methodology to choose the bestcontent of Micronise silica gel, acidifying agent and disintegrating agent. For the qualitystandards part, The system of quality contol was established, Using Ultravioletspectrophotometry as the identification method and HPLC as the qualification method. Thedetermination of dissolution system was established. And The stability was inspected.Result: The dispersible tablets were prepared by wet granulation method. The bestdisintegrating agent was the mixture of CMS-Na and PVPP. According to the result ofcentral composite design-response surface methodology,3batches of Gefitnib dispersibletablets were made.The specific analysis method was established, the linear range wasformed from0.8to4.8μg·mL-1(R2=0.9999). The Low、 medium and high recovery were100.32%、100.22%、101.12%.Both the relative standard deviation(RSD) of within-day and day-to-day were less than1%. The method was simple and accurate. The condition ofdissolution test in vitro:3%tween80water solution1000mL as disso medium; resolutionrate is50rmp/min and the bath temperature is37℃±0.5℃. The linear range was from2.5to30μg·mL-1(R2=0.9996), and the Low、 medium and high recovery were100.74%、100.29%、100.64%. Both the relative standard deviation(RSD) of within-day andday-to-day were less than1%. The stability result indicated that this formula was stable,moisture resistance.Conclusion The Gefitinib formula preparation method established in this study was stableand feasible. And the analysis method could efficiently control the quality of the product.