A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.
1 July 1998 in Bulletin of the Chemical Society of Japan
Deoxycholic acid (DCA) was ground with a guest compound by using a vibrational mill. Powder X-ray diffraction, differential scanning calorimetry, and fluorescence spectroscopic data indicated the formation of the inclusion complex in the ground mixture of DCA–phenanthrene and DCA–naphthalene systems. The DCA–naphthalene ground mixture was found to have higher crystallinity than the DCA–phenanthrene ground mixture, and this was assumed to relate to the difference in the crystallization temperature of the inclusion complex. When low-temperature grinding was performed for DCA and other aromatic hydrocarbons along with naphthalene and phenanthrene, all the ground mixtures were obtained in amorphous state. Crystallization of inclusion compounds from the amorphous ground mixtures was observed to occur at a higher temperature as the stoichiometric ratio (DCA/guest) of the compound increased. With regard to the formation of crystalline complex between DCA and a guest, such as naphthalene, by grinding at room temperature, a two-step mechanism was proposed: i.e., (i) amorphization of both DCA and guest crystals, and (ii) crystallization of the inclusion complex induced above a certain temperature.