Assessment of Small Volume (250-mL) Vessels for Use in Biorelevant Dissolution

Introduction:In vitro biorelevant dissolution is an important tool for pharmaceutical development and formulation evaluation.Standard United States Pharmacopeia (USP) 1-L vessels and the paddle apparatus have been commonly used for biorelevant dissolution tests, including tests in a small volume (250 mL) of medium.When Chinese small volume (CSV) vessels (250-mL) became available and were described in the Chinese Pharmacopeia <931>, it was uncertain if biorelevant dissolution profiles obtained with the CSV vessel are comparable to those obtained with the standard USP vessel.Methods: To evaluate the two types of the vessels for biorelevant dissolution testing, a particle dissolution model was developed using computational fluid dynamics (CFD), the Noyes-Whitney equation, and experimental parameters, and a scaling factor (Sherwood number) was calculated using the model.A paddle speed for the CSV vessel setup that correlate with the USP vessel configuration was determined by the model using similar Sherwood numbers.The dissolution model was verified using USP Prednisone Tablets RS in 250 mL of water, then further verified using two proprietary drugs in 250 mL of biorelevant medium (fasted state simulated intestinal fluid).Results: The model predicted that the dissolution profile generated at 84 rpm in the CSV vessel would match that obtained at 50 rpm in the USP vessel.Indeed, similar dissolution profiles were obtained with both types of vessels under these conditions.Conclusion: This study demonstrated that by using a suitable scaling factor for agitation, CSV vessels for biorelevant dissolution in FaSSIF can generate similar results with standard 1-L USP vessels.