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An in vitro kinetic method for detection of precipitation of poorly soluble drugs
Zimei Wu1, Ian G Tucker, Majid Razzak
1School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.
Abstract:
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 (Tonset), maximum rate (Vmax) and the time to reach Vmax (Tmax). 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 degrees C compared with 25 degrees 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.
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