Ylp-17005 Tablets Optimized Formulation And Human Bioequivalence Study

ObjectiveYLP tablets are a new generation of non-nucleoside reverse transcriptase inhibitors against HIV-1 virus.They are used alone or in combination with other drugs to treat HIV infection.YLP is a poorly soluble drug with low bioavailability and low correlation in vivo and in vitro,it is difficult to go to imitation.When the paper was formulated,there was no YLP film that passed the consistency evaluation in China.The main purpose of this project is to develop a generic drug that is consistent with the quality,efficacy,and safety of the original developer（YLP-R tablet）and is suitable for commercial production.Develop quality standards and try to find the most discriminating dissolution profile by using data in vitro and in vivo.MethodsThrough research literature and analysis of the original development agent,select appropriate raw materials and auxiliary materials,develop and optimize the small test prescription and preparation process of ylp-17005 in the laboratory.Under the conditions of GMP,continue to explore the process parameters and prescriptions of commercial scale-up production,and confirm the parameters to carry out verification of three consecutive batches of commercial production processes.Through the bioequivalence evaluation of one of the batches and the original developer,the prescription process was adjusted again until it was equivalent to the original developer,and the quality of the product was determined by using the produced product to determine the quality standard of ylp-17005.ResultsAfter three trials of process development and human bioequivalence test,this experiment developed a YLP-T tablet imitation preparation that is consistent with the original quality index of the original development agent in vitro,and the stability test results of 6 months showed that the repeatability and stability of the process are good,and the registration data has been submitted to the National Food and Drug Evaluation Center in 2018.Through the human bioequivalence test,it was found that the AUC_0-72of test preparation（YLP-T）and the original preparation（YLP-R）were（67131.429±16632.323）ng·h·m L^-1,（63867.228±16973.293）ng·h·m L^-1,C_maxwere（3432.407±968.898）ng·m L^-1,（3298.197±836.457）ng·m L^-1,and T_maxwas（3.074±1.231）h,（2.791±1.118）h,respectively.The 90%confidence interval of the geometric mean ratio（test preparation/reference preparation）of C_maxand AUC_0-72under fasting administration was within the acceptable equivalent range（80.00%～125.00%）,respectively,96.60%～111.31%,100.76%～109.80%.After double-sided t-test analysis,the P value was less than 0.05,then H0 was rejected to receive H1,that is,the two preparations were bioequivalent under the conditions of fasting administration of the test.ConclusionThe YLP-T imitation preparation developed by this subject meets the requirements of the relevant guidelines for conformity evaluation issued by the CFDA.It can replace the original development agent,the quality standard is reasonable,and the quality of the preparation can be well controlled.