Research On Preparation Technology And Quality Control Of Gefitinib Tablets

Gefitinib is developed by AstraZeneca company for the treatment ofadult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR-TK. It was approved by EMEA and marketed in several European countries. It was approved for marketing by SFDA in China in2007. And the dosage form is tablet, with specifications of0.25g. Currently, Gefitinib has not been listed in the generic drug product yet. This study was to investigate the formula and preparation technology of generic Gefitinib Tablets, as well as the produt quality control and stability, and to determine the feasibility of the formula and preparation technology. This study will provide reliable basis for the industrial production of generic Gefitinib Tablets. The research contents include:(1) Prescription Study of Gefitinib TabletsThe formula were determined by prescription screening, scale-up of small test, and pilot scale experiments using dissolution curve as the main indicators. Prescription composition (1000) is as follows:gefitinib250g, lactose monohydrate150g, microcrystalline cellulose50g, cross-linked sodium carboxymethyl cellulose20g, povidone K3022.5g,2.5g sodium dodecyl sulfate, magnesium stearate5g, coating weight of approximately2%.(2) Preparation Technology of Gefitinib TabletsGefitinib Tablets were prepared by wet granulation tabletting. Focus on the effects of drug substance particle size and hardness of a tablet formulation using appearance, disintegration time, hardness and dissolution as indicators. After three batches of small scale and pilot scale tests to determine the preparation of gefitinib tablets.(3) Quality Control of Gefitinib TabletsMethodology researches were carried out to establish the method for determination of the content and related substances of Gefitinib Tablets by HPLC, and determination of dissolution by UV. The results showed that the methods are specific, accurate, sensitive and controllable.(4) Stability of Gefitinib TabletsResults related to factors experiment, accelerated test (6months), intermediate test at30℃(12months), and long-term test at25℃(12months) showed that there were no significant changes for the appearance of the product, related substances, dissolution, and content during the whole testing period. These results clearly indicate the good stability of the product.