Study On Formulation And Preparation Of Ledipasvir-sofosbuvir Combination Tablet

Ledipasvir-Sofosbuvir combination tablet(LSCT),Harvoni,is the first FDA-approved interferon-and ribavirin-free regimen to treat genotype 1hepatitis C.The purpose of this paper is to study the formulation and preparation of LSCT with reference to the originator product(Harvoni TM).The formulation and small-scale preparation technology of LSCT were studied according to the quality standard of Harvoni,then the technology for pilot-scale preparation was optimized and verified.The basic processes for the preparation of LSCT were developed according to the patent of Harvoni and included two successive processes.First,ledipasvir solid-dispersion was prepared to increase the solubility of ledipasvir;then,LSCT was prepared using dry granulation method.The type and amount of excipients was selected based onthe package insert of Harvoni and the results of drug-excipient compatibility testing and dissolution testing.The optimized formulation was then developed.Three consecutive,pilot-scale batches of LSCT were prepared and subjected to the quality evaluation.The results showed that the developed LSCT met the quality standards of Harvoni,which indicated achievement of the study purpose.