Rapid throughput solubility screening method for BCS class II drugs in animal GI fluids and simulated human GI fluids using a 96-well format.
A rapid solubility-screening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug development process, minimizes GI fluid needs, and produces in vitro solubility information with potential in vivo implications. A number of BCS II drugs were dissolved in DMSO at approximately 40 mM, and robotically distributed to a 96-well plate. The DMSO was evaporated and drugs were equilibrated with selected GI fluids, both fed and fasted states. After equilibration, precipitated wells were subjected to HPLC analysis. A spreadsheet calculated solubility automatically from HPLC output. Intra-day, inter-day, and inter-plate reproducibility were within 15% RSTD for the tested drugs with the primary source of variability being injection precision of our injector system. The reported solubility from screening assays was well correlated with literature data (r(2) = 0.80) with a slope of 0.86 and (r(2) = 0.99) with a slope of 0.89. This screening assay converts conventional solubility measurements to a 96-well format for increased throughput (>12 samples/h), reduces fluid needs, and minimizes drug consumption.
Guo
Jeremy
J
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA. jeremyguo@hotmail.com
Elzinga
Paul A
PA
Hageman
Michael J
MJ
Herron
James N
JN
D000818:Animals; D001702:Biopharmaceutics / Q000379:methods*; D001826:Body Fluids / Q000378:metabolism; D005374:Filtration; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000145:classification*; D015203:Reproducibility of Results; D012995:Solubility
D004364:Pharmaceutical Preparations