Research And Development Of Tenofovir Disoproxil Fumarate Tablets

Objective: Tenofovir Disoproxil Fumarate(TDF), C19H30N5O10 P.C4H4O4, white to white crystalline powder, is a new kind of nucleoside reverse transcriptase inhibitors, used in the treatment of adult human immunodeficiency virus(HIV) infection or Hepatitis B virus(HBV)infection. This product is a prodrug to tenofovir effect in the body; Biopharmaceutics classification: class III, high solubility, low permeability.In 2001, Tenofovir Disoproxil Fumarate tablets goes on sale in the United States by Gilead Sciences Inc., mainly used in the treatment of HIV infection, and can combination with other antiretroviral drugs, has the very good anti HBV activity. It was approved to use in the treatment of hepatitis B virus by the EU in April 2008 and FDA in August 2008. It is one of the best drug hepatitis B.The research, based on the concept of quality of risk management(ICHQ8\9\10\11)and Quality by Design, aims to ensure the stability of the product and the bio-equivalent with the control drug, through the reference of the original product agents, prescription screening using dissolution uniformity in the process, at the same time with USP standard strictly control the quality of drug substances and drug products.Methods: Choose the excipients of the content and determine the specific proportion of the excipients through experimental research, and determine the content formulation according to the results.The emphasis of the preparation study focuses on the control of critical process steps. Through designing the experimental research and referring to the device usage experience, useing Mintab data analysis, ultimately determine the preparation process parameters and the corresponding in-control parameters.During the process of establishing the quality standard, the character, dissolution inspection, related substance and the proposed method for the determination of the content would refer to the USP Pending Monograph Draft 1-For Public Comment Tenofovir Disoproxil Fumarate Tablets.Conduct the influence factor test according to the Guidelines of the stability study of chemicals, and detect the important items for stability using the quality standard to determine the drug stability.Results: The finally determined formulation of the content: Tenofovir Disoproxil Fumarate as active ingredient, Lactose as the filler, microcrystalline cellulose as the filling agent,gel starch and 50% ethanol as binder, crosslinking carboxymethyl cellulose as disintegrating agent, magnesium stearate as lubricant, coating powder with good product that has made.Through the systematic quality research, ultimately determine the quality standards, and conduct the influence factor test study using the batche of the small-scale samples with the proposed standard.The result of the influence factors shows that: Tenofovir Disoproxil Fumarate Tablets are sensitive in the conditions of high temperature, high humidity, high light, acidic environment, and alkaline environment.Conclusion: Through the studies on formulation screening and preparation process, both the product formulation and the production process parameters are determined. And the preparations of one batches of small-scale sample is completed. The results show that qualified products can be produced by adopting the proposed formulation and process parameters.Through the study on the method of the related substances and the dissolution inspection, the quality standard is ultimately determined, and the test results show that the quality of the batches of small-scale samples meets the standard requirements. As seen from the stability data, Tenofovir Disoproxil Fumarate Tablets are sensitive in the conditions of high temperature, high humidity, high light, acidic environment, and alkaline environment.In summary, with the reasonable design of the formulations, feasible process route and analytic methods, good product reproducibility, reasonable quality standard and qualified inspection of the small-scale samples, impurities being controllable, the results of this study can be used for pilot-scale production.