Novel Application of MRI Technique Combined with Flow-Through Cell Dissolution Apparatus as Supportive Discriminatory Test for Evaluation of Controlled Release Formulations

摘要

Dissolution studies cannot distinguish phenomena occurring inside the dosage forms when studying formulation with similar dissolution profiles—such formulations can behave differently when considering their physical changes. The application of flow-through dissolution apparatus integrated with magnetic resonance imaging (MRI) system for discriminative evaluation of controlled release dosage forms with similar dissolution profiles was presented. Hydrodynamically balanced systems (HBS) containing l-dopa and various grades hydroxypropyl methylcelluloses were prepared. The dissolution studies of l-dopa were performed at high field (4.7 T) MR system with MR-compatible flow-through cell. MRI was done with 0.14 × 0.14 × 1-mm spatial resolution and temporal resolution of 10 min to record changes of HBS parameters during dissolution in 0.1 M HCl. Structural and geometrical changes were evaluated using the following parameters: total area of HBS cross-section, its Feret’s diameter, perimeter and circularity, area of hydrogel layer, and “dry core” area. While the dissolution profiles of l-dopa were similar, the image analysis revealed differences in the structural and geometrical changes of the HBS. The mechanism of drug release from polymeric matrices is a result of synergy of several different phenomena occurring during dissolution and may differ between formulations, yet giving similar dissolution profiles. A multivariate analysis was performed to create a model taking into account dissolution data, data from MRI, information about chemical structure, and polymer viscosity. It provided a single model for all the formulations which was confirmed to be competent. The presented method has merit as a potential Process Analytical Technology tool.