Hydrodynamics of the small vessel as described in the Chinese Pharmacopoeia

Abstract

Small volume dissolution systems are commonly used in dissolution testing, primarily in method development for low dose formulations compared to standard dissolution apparatuses used with evaluation of larger formulations. This is typically done because of cost savings associated with using smaller media volumes and sample sizes, to overcome the lack of material in early development, and to provide higher analytical sensitivity and discrimination ability. The Chinese Pharmacopoeia (CP) includes a small dissolution apparatus in their list (“Method 3 (Small Vessel)”) (The State Pharmacopoeia Commission of P.R. China (2015a). 0931 Dissolution and Drug Release Test). Currently, limited information is available in the literature on the dissolution performance of small apparatuses in general and the CP small apparatus in particular (referred to here as Chinese Small Vessel System (ChSVS)). Therefore, the objective of this work was to experimentally investigate the hydrodynamics in the ChSVS operating at different paddle agitation speeds (35–100 rpm) using Particle Image Velocimetry (PIV). Results indicated that the flow field in the ChSVS is mostly dominated by the tangential velocities. Axial velocities and radial velocities are typically one or two orders of magnitude lower than the tangential velocities. The non-dimensional velocity profiles, scaled with the paddle tip speed, are generally self-similar, implying that the velocities in most regions of the ChSVS are directly proportional to the paddle rotational speed. The hydrodynamics in ChSVS is extremely sensitive to even minute deviations from perfect symmetry about the vertical centerline. This work provides a significant insight into the flow inside the ChSVS and is expected to be of relevance for scientists and practitioners developing new dissolution methods and working in the dissolution testing area.