Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes

Abstract

The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH 6) and acidic (pH 2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (E a) values calculated from caffeine diffusivities were in the range of Fickian transport (20-40 kJ mol-1). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer-Peppas model would indicate anomalous transport. However, the low apparent Ea values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent Ea values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true Ea would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion-erosion mechanism, both at pH 6 and 2.