The influence of medium flow on gel formation and drug release in xanthan matrix tablets

Matrix tablets made of hydrophilic polymers like xanthan are widely used for controlled delivery of drugs. As medium penetrates the matrix, the outer surface of the tablet hydrates and swells, forming a gel coat around the dry central core. The swelling starts with medium penetration into the matrix where the polymer concentration gradient is formed in the tablet, starting at a high concentration in the more or less dry core and declining through the gel layer towards the gel interface. As medium penetrates into the tablet a penetration front, that is the border between dry and hydrated glassy polymer, is moving into the tablet. When medium concentration is high enough, a phase transition from hydrated glassy polymer into rubbery state occurs at the swelling front position. The border between gel layer and medium is denoted as an erosion front. Drug release from such a system depends on drug characteristics and the gel layer properties and is controlled by drug diffusion through the gel layer, purely by the gel erosion or a combination of both.
In the study the gel thicknesses of pure xanthan tablets and of xanthan tablets with 50% pentoxifylline drug in static conditions and under medium flow around the tablet surface were measured by combination of different MRI techniques (2D multi-echo sequence, 1D SPI and 1D SPI T2 mapping) in water and in HCl pH 1.2 medium. The tablet was inserted in a container, so that only one circular surface was exposed for medium penetration. For the measurements in static conditions the medium was added to the tablet just before the sequential MR measurements started. For the experiments with flow, the container with the tablet was connected via plastic hoses to a reservoir of medium and an electric pump that drove the medium through the container. The combination of MRI sequences was performed every 30 minutes for 12 hours. The results show that the medium flow does not affect the medium penetration into the tablet and the position of the swelling front, but it changes the position of erosion front owing to increased polymer erosion causing by mechanical forces of streaming medium on the tablet surface. The impact of flow was more pronounced in water than in acid medium showing the formation of stronger gel in acid medium. The results agree with the drug release studies which show that release of highly soluble pentoxifylline drug is significantly increased at higher mechanical forces in water medium, where the main release mechanism is polymer erosion, while in acid medium, where the main release mechanism is drug diffusion, the effect is negligible.