Simultaneous probing of swelling, erosion and dissolution by NMR-microimaging – Effect of solubility of additives on HPMC matrix tablets
Artikel i vetenskaplig tidskrift, 2009
Extensive studies of extended release tablets based on hydrophilic polymers have illuminated several
aspects linked to their functionality. However, in some respects key factors affecting the mechanisms
of release are yet unexplored. In the present study, a novel NMR-microimaging method has been used
to study the influence of the solubility of additives in extended release hydroxypropyl methylcellulose
(HPMC) matrix tablets. During the course of the tablet dissolution the movement of the swelling and
erosion fronts were studied simultaneously to the release of both polymer and additives. Moreover,
the focused beam reflectance measurement (FBRM) technology was for the first time assessed for both
release and dissolution rate studies of poorly soluble particles. The studied formulations comprised solely
HPMC, 40% HPMC and 60% mannitol (Cs = 240 mg/ml) and 40% HPMC and 60% dicalcium phosphate (DCP)
(Cs = 0.05 mg/ml). The dissolution rate of the tablets was highest for the HPMC/mannitol formulation,
followed by HPMC/DCP and plain HPMC tablet. A contrasting order was found regarding the degree and
kinetics of swelling. The results were interpreted in light of how the mass transport in the gel layer is
influenced by the solubility of additives. A mechanistic model, considering osmotic pressure gradient and
the effective diffusion of the dissolution medium in the gel is proposed.