Abstract

A quantitative PGSE-RARE pulse sequence was developed and successfully applied to the in situ dissolution of two pharmaceutical formulations dissolving over a range of timescales. The new technique was chosen over other existing fast velocity imaging techniques because it is T2 weighted, not T2∗ weighted, and is, therefore, robust for imaging time-varying interfaces and flow in magnetically heterogeneous systems. The complex signal was preserved intact by separating odd and even echoes to obtain two phase maps which are then averaged in post-processing. Initially, the validity of the technique was shown when imaging laminar flow in a pipe. Subsequently, the dissolution of two drugs was followed in situ, where the technique enables the imaging and quantification of changes in the form of the tablet and the flow field surrounding it at high spatial and temporal resolution. First, the complete 3D velocity field around an eroding salicylic acid tablet was acquired at a resolution of 98×49μm2, within 20min, and monitored over ∼13h. The tablet was observed to experience a heterogeneous flow field and, hence a heterogeneous shear field, which resulted in the non-symmetric erosion of the tablet. Second, the dissolution of a fast dissolving immediate release tablet was followed using one-shot 2D velocity images acquired every 5.2s at a resolution of 390×390μm2. The quantitative nature of the technique and fast acquisition times provided invaluable information on the dissolution behaviour of this tablet, which had not been attainable previously with conventional quantitative MRI techniques.

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