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

• Published in: International journal of pharmaceutics Vol. 304; no. 1; pp. 1 - 3
• Main Authors: Wu, Zimei, Tucker, Ian G., Razzak, Majid, Medlicott, Natalie J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.11.2005; Elsevier
• Subjects: Albendazole - analogs & derivatives; Albendazole - chemistry; Biological and medical sciences; Chemical Precipitation; Drug Stability; General pharmacology; Kinetic precipitation detection; Kinetics; Medical sciences; Microtiter plate reader; Onset time; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poorly soluble drugs; Ricobendazole; Solubility; Technology, Pharmaceutical - methods; Turbidity; Poorly soluble drugs; Kinetic precipitation detection; Microtiter plate reader; Ricobendazole; Onset time; Turbidity; Drug; Precipitation; Pharmaceutical technology; Kinetic precipitation detection; Microtiter plate reader; Poorly soluble drugs. Turbidity; Onset time; Kinetic method; Kinetics; Detection; In vitro
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.08.012

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.