The Research And Development Of Sorafenib Tosylate Tablets

Sorafenib is an oral multitargeted, multi-kinase inhibitor, literature shows that it can inhibit the proliferation of tumor cells and anti-angiogenic effects.Sorafenib is the world’s first oral multi-kinase inhibitor, besides, there are no potent drugs for treating liver cancer on market currently, it has important significance on the treatment of the patients with inoperable terminal liver cancer.Objective:To obtain the prescription and processes which can product Sorafenib Tosylate Tablets smoothly by experiments. The products with this prescription and processes should be stable and controllable,and has the same quality with reference preparations.Methods: Pre-study of the prescription Through the study on physicochemical properties of raw materials, as well as the original research drug disclosed label by the US Food and Drug Administration(FDA) and patent research, initially identified the sorafenib tosylate tablets excipients for microcrystalline cellulose, crosslinking sodium carboxymethyl cellulose,propylene carboxy methyl cellulose, sodium dodecyl sulfate, magnesium stearate. Based on the study of the dissolution curve of the foreign market, the dissolution medium and the method of dissolution for the selection of the prescription were determined.Screening of prescription Through the screening and optimization dosage of filler, disintegrant, adhesive, lubricant,we determined the wet granulation production process as the main body of the tablet. Microcrystalline cellulose(pH301) is as filling agent, Cross-linked sodium carboxymethyl cellulose as a disintegration agent,Carboxymethyl cellulose(E5) as a binder, twelve alkyl sodium sulfate as a wetting agentMagnesium stearate as lubricant. To further determine the prescription process through the pilot test. Through repeated experiments and demonstrations, and ultimately determined the sorafenibtosylate tablet prescription. The preparation process has 4 steps: crushing API,preparing granules, preparing tablet cores and film coating.Quality research and quality specifications According to the State Food and drug supervision and administration regulations, the products were studied comprehensively. Based on domestic and foreign related guidelines and quality standards, the characteristics of the three batches of continuous production were studied and the quality standard was established.Stability study Self-made sorafenib tosylate tablets were influencing factors experiment. The results showed that the product in the light shine(4500lx ± 500 LX), high temperature(60℃) and high humidity(92.5%RH)placed 10 days,the quality test items in accordance with the provisions, so the product has no special requirements on storage conditions. Then performed Accelerated test, long-term test, the results showed that the product was at 40±2℃/75%±5%RH for 6 months and at 25±2℃/60%±10%RH for 6 months,the quality indicators were not significantly changed and complied with the quality specifications. It is proved that the product is stable in 6 months at room temperature.Conclusions: Through the comparison of the self-made product with RLD research, and the stability test results showed that the quality of each point of stability was basically balanced, the test method could accurately and effectively reflect the real degradation of the sample, which reflected the consistency between the sample and the control drug, and reached the purpose of drug development.