title: Prediction of in vivo drug performance using in vitro dissolution coupled with STELLA: a study with selected drug products.
abstract: Prediction of the in vivo performance of the drug product from the in vitro studies is the major challenging job for the pharmaceutical industries. From the current regulatory perspective, biorelevant dissolution media should now be considered as quality control media in order to avoid the risk associated. Physiological based pharmacokinetic models (PBPK) coupled with biorelevant dissolution medium is widely used in simulation and prediction of the plasma drug concentration and in vivo drug performance. The present investigation deals with the evaluation of biorelevant dissolution media as well as in vivo drug performance by PBPK modelling using STELLA® simulation software. The PBPK model was developed using STELLA® using dissolution kinetics, solubility, standard gastrointestinal parameters and post-absorptive disposition parameters. The drug product selected for the present study includes Linezolid film-coated immediate-release tablets (Zyvox), Tacrolimus prolonged-release capsules (Advagraf), Valganciclovir tablets (Valcyte) and Mesalamine controlled-release capsules (Pentasa) each belonging to different biopharmaceutics classification system (BCS). The simulated plasma drug concentration was analyzed and pharmacokinetic parameters were calculated and compared with the reported values. The result from the present investigation indicates that STELLA® when coupled with biorelevant dissolution media can predict the in vivo performance of the drug product with prediction error less than 20% irrespective of the dosage form (immediate release versus modified release) and BCS Classification. Thus, STELLA® can be used for in vivo drug prediction which will be helpful in generic drug development.
authors.affiliation: a Centre of Excellence-Biostudies , Integrated Product Development Organization, Dr. Reddy's Laboratories , Hyderabad , Andhra Pradesh , India.
authors.forename: Sumon
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: a Centre of Excellence-Biostudies , Integrated Product Development Organization, Dr. Reddy's Laboratories , Hyderabad , Andhra Pradesh , India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Yadav
authors.affiliation: a Centre of Excellence-Biostudies , Integrated Product Development Organization, Dr. Reddy's Laboratories , Hyderabad , Andhra Pradesh , India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Aggarwal
mesh_terms: D002214:Capsules / Q000737:chemistry; D003198:Computer Simulation; D065546:Drug Liberation; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D000069349:Linezolid / Q000737:chemistry; D019804:Mesalamine / Q000737:chemistry; D008954:Models, Biological; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D016559:Tacrolimus / Q000737:chemistry; D000077562:Valganciclovir
chemical_list: D002214:Capsules; D013607:Tablets; D019804:Mesalamine; D000077562:Valganciclovir; D000069349:Linezolid; D015774:Ganciclovir; D016559:Tacrolimus
keywords: BCS classification; Biorelevant dissolution media; PBPK modelling; STELLA