MRI Studies of the Hydrodynamics in a USP 4 Dissolution Testing Cell

作者：Shiro G; Gladden L F^*; Sederman A J; Connolly P C; Butler J M

来源：Journal of Pharmaceutical Sciences, 2011, 100(3): 976-991.

DOI：10.1002/jps.22343

• hydrodynamics
• USP apparatus 4 (flow-through cell)
• magnetic resonance imaging (MRI)
• dissolution testing
• laminar flow
• physical characterization
• in vitro models
• dissolution
• in vitro-in vivo correlations (IVIVC)
• controlled release

We present a detailed study of hydrodynamics inside the flow-through dissolution apparatus when operated according to USP recommendations. The pulsatile flow inside the flow-through cell was measured quantitatively using magnetic resonance imaging (MRI) at a spatial resolution of 234 x 234 mu m(2) and slice thickness of 1 mm. We report the experimental protocols developed for in situ MRI studies and the effect that the operating conditions and tablet orientation have on the hydrodynamics inside commercial flow cells. It was found that the flow field inside the dissolution cells was, at most operating conditions, heterogeneous, rather than fully developed laminar flow, and characterised by re-circulation and backward flow. A model tablet was shown to be contacted by a wide distribution of local velocities as a function of position and orientation in the flow cell. The use of 1 mm beads acted as a distributor of the flow but did not suffice to ensure a fully developed laminar flow profile. These results emphasise the necessity to understand the influence of test conditions on dissolution behaviour in defining robust flow-through dissolution methods.

• 出版日期2011-3