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 criticalto release robustness.Methods. The release of HPMC and additives was studied using a modified USP II method at two paddlestirring 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 therelease from the HPMC/mannitol tablets. Below this point the matrix rapidly disintegrated in a non robustmanner. At higher HPMC contents the mannitol release became increasingly diffusion controlled withmaintained matrix integrity. The release robustness was lower for HPMC/DCP than HPMC/mannitoltablets at high HPMC contents, however, lacking critical points. The critical point was interpreted as thepercolation 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 anerosion 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 thepercolation threshold becomes vital for maintaining the release robustness