An in vitro kinetic method for detection of precipitation of poorly soluble drugs

A simple in vitro method for the detection of precipitation using 96-well microplates and a SpectraMax Plus microtiter plate reader has been developed and described. The method requires only small amount of drug and is, therefore, potentially applicable in early pre-formulation. The method is based on opacity changes that occur with precipitation and yields several descriptive parameters, onset time ( T onset), maximum rate ( V max) and the time to reach V max ( T max). Using these parameters, potential parenteral formulations can be ranked by their tendency to precipitate on dilution. We report use of this method and ranking of potential formulations of ricobendazole (RBZ), a poorly soluble anthelmintic, in various solvent systems. Detection at 500 nm was more sensitive than a wavelength of 550 nm and increased temperature (37 °C compared with 25 °C) accelerated precipitation. Results demonstrated the method was simple, descriptive and objective in the detection of precipitation of ricobendazole formulation on dilution and pH shift.