Predicting drug release from solid pharmaceutical dosage forms using quantitative multi-nuclear (¹H- ¹⁹F) magnetic resonance micro imaging

This paper presents our recent work concerning the application of quantitative ¹H RARE imaging, ¹⁹F radial FLASH imaging and simple ¹H/¹⁹F profiling to study: (i) controlled release drug delivery devices during dissolution testing in a MRI compatible USP-IV dissolution cell under pharmacopeial conditions and; (ii) non-swelling silicone elastomer based materials pre-loaded with active pharmaceutical ingredient (API) via solvent uptake. For (i), quantitative maps of absolute water concentration, T₂ relaxation time, water self-diffusivity, D, and dissolution cell hydrodynamics maps can be obtained in less than three minutes each, allowing a thorough overview of the tablet dissolution process. For hydroxypropylmethyl cellulose (HPMC) polymer based tablets containing the antipsychotic trifluoperazine dihydrochloride (TDFH) API, correlations between water concentration maps and spin-spin relaxation time maps allow us to quantify and visualise the separation of the dry polymer core, swollen glassy layer and gel layer of the swollen HPMC/TDFH compact. In addition to the ¹H RARE studies, 2D ¹⁹F FLASH techniques with radial sampling of k-space were used to obtain images of the distribution of the ¹⁹F containing API during dissolution of the same samples. Figure 1 shows that the co-registration of the API via the ¹⁹F TDFH map and polymer mobility via the water ¹H T₂ relaxation time maps allows us to visualise the API egress and water ingress into the polymer matrix simultaneously; thus API diffusion and distribution can be tracked unambiguously with regard to the evolving gel structure of the tablet.

These results further show that the swelling front in the water ¹H T₂ relaxation time maps matches the API diffusion front from the ¹⁹F images. This observation suggests the API becomes hydrated but remains immobilised in the swollen glassy layer. In a related study, the potential of ¹H and ¹⁹F 1D-MR profiling is further highlighted as a tool to predict API release from non-swelling silicone elastomer based dosage forms. The uptake of two different APIs, 4-fluorophenylalanine and the less polar ciprofloxacin, into silicone elastomers via a solvent loading method was examined by both ¹⁹F and ¹H 1D profiling. The MR data was then correlated to: (a) API uptake using conventional solvent mass uptake data and: (b) API release using UV-vis measurements. The results show that the ¹⁹F profiles provide a much better predictor of API release behaviour than the ¹H profiles.