9 research outputs found
The Impact of Dose and Solubility of Additives on the Release from HPMC Matrix Tablets-Identifying Critical Conditions
Purpose. The dissolution of HPMC matrix tablets containing different amounts of highly soluble
(mannitol) or poorly soluble (dicalcium phosphate, DCP) was studied to deduce the parameters critical
to release robustness.
Methods. The release of HPMC and additives was studied using a modified USP II method at two paddle
stirring rates, 50 and 125 rpm, at HPMC content varying from 15% to 100%.
Results. At HPMC contents between 30% and 35% a critical point was identified and found crucial to the
release from the HPMC/mannitol tablets. Below this point the matrix rapidly disintegrated in a non robust
manner. At higher HPMC contents the mannitol release became increasingly diffusion controlled with
maintained matrix integrity. The release robustness was lower for HPMC/DCP than HPMC/mannitol
tablets at high HPMC contents, however, lacking critical points. The critical point was interpreted as the
percolation threshold for HPMC and differences explained in terms of water transport into the matrix.
Conclusion. The release robustness was lower for formulations with additives of low solubility having an
erosion controlled release than for additives with higher solubility and a diffusion controlled release.
However, for additives creating a steep osmotic pressure gradient, an HPMC content above the
percolation threshold becomes vital for maintaining the release robustness
Simultaneous probing of swelling, erosion and dissolution by NMR-microimaging – Effect of solubility of additives on HPMC matrix tablets
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
Real time MRI to elucidate the functionality of coating films intended for modified release
Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1H and 19F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods
Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study
The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Ficḱs law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices