International Journal of Pharmaceutics 304 (2005) 1–3 Rapid communication An in vitro kinetic method for detection of precipitation of poorly soluble drugs Zimei Wu a , Ian G. Tucker a , Majid Razzak b , Natalie J. Medlicott a,∗ a School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand b Bomac Laboratories Limited, Auckland, New Zealand Received 21 January 2005; received in revised form 8 August 2005; accepted 15 August 2005 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 (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. © 2005 Elsevier B.V. All rights reserved. Keywords: Kinetic precipitation detection; Microtiter plate reader; Poorly soluble drugs; Turbidity; Onset time; Ricobendazole Post-injection precipitation is an important concern for poorly soluble drugs formulated as injections at low or high pH or with co-solvent solubilisation. Drug precipitation tends to occur with pH neutralisation or co-solvent dilution by blood or extracellular fluid. Problems caused by drug precipitation at injection sites include pain on injection, inflammatory reactions and ∗ Corresponding author. Tel.: +64 3 4795919; fax: +64 3 4797034. E-mail address: natalie.medlicott@stonebow.otago.ac.nz (N.J. Medlicott). sometimes reduced drug bioavailability (Yalkowsky et al., 1998). Various in vitro methods have been developed to study precipitation of parenteral formu- lations, e.g. the dynamic injection model (Yalkowsky et al., 1983) and static serial dilution model (Li et al., 1998). Precipitation is determined by eye or by mea- suring opacity spectrophotometrically at wavelengths between 400 and 500 nm. In the dynamic method, the formulation is added into buffer or an infusion fluid through a specifically designed injector. Both flow rates can be adjusted to simulate the precipitation event 0378-5173/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2005.08.012