title: Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems.
abstract: With recent advances in the development of supersaturating oral dosage forms for poorly water-soluble drugs, pharmaceutical scientists are increasingly applying in vitro dissolution testing under non-sink conditions for a direct evaluation of their ability to generate and maintain supersaturation as a predictive surrogate for ensuring product quality and in vivo performance. However, the scientific rationale for developing the appropriate non-sink dissolution methodologies has not been extensively debated. This calls for a comprehensive discussion of recent research efforts on theoretical and experimental considerations of amorphous solubility, liquid-liquid phase separation, and phase transitions of drugs in a supersaturated solution when dissolution testing is performed under supersaturated non-sink conditions. In addition, we outline the concept of "sink index" that quantifies the magnitude of deviations from perfect sink dissolution conditions in the sink/non-sink continuum and some considerations of non-sink dissolution testing for marketed drug products. These factors should be carefully considered in recommending an adequately discriminatory dissolution method in the performance assessment of supersaturating drug delivery systems.
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Dajun D
authors.initials: DD
authors.lastname: Sun
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907. Electronic address: lstaylor@purdue.edu.
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D007408:Intestinal Absorption; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards; D044367:Phase Transition; D011786:Quality Control; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
keywords: amorphous solid dispersions; dissolution; non-sink; precipitation; supersaturation