ABSTRACT
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.
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Acknowledgments
The authors acknowledge AstraZeneca and Swedish Knowledge Foundation (particularly the YPK-project) for funding this work. Sincere thanks to Anders S. Carlsson and Jonas Johansson at AstraZeneca for their advisory and technical assistance with the analytical methods (LC-MS) and FBRM-technology, respectively.
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Tajarobi, F., Abrahmsén-Alami, S., Hansen, M. et al. The Impact of Dose and Solubility of Additives on the Release from HPMC Matrix Tablets—Identifying Critical Conditions. Pharm Res 26, 1496–1503 (2009). https://doi.org/10.1007/s11095-009-9861-y
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DOI: https://doi.org/10.1007/s11095-009-9861-y