Water uptake and force development in an optimized prolonged release formulation

Abstract

A new prolonged release oral tablet has recently been developed. The formula, which contains an antiinflammatory agent (diclofenac sodium), two inert polymers (polyvinylchloride and ethylcellulose) and two lubricants (magnesium stearate and talc), was optimized as far as the manufaturing process was concerned. The outcome was the selection of a few optimized tablets, which were obtained by different processes (direct compression, double compression, compaction of the five raw materials, separate compaction of the drug and polyvinylchloride and wet granulation). From a biopharmaceutical point of view the response variables of major interest were dissolution profile and the variability of dissolution. In the present work, with the aim of elucidating the mechanisms of drug release, water penetration and force development measures were undertaken on the optimized tablets and related to porosimetry data. Differences between the various tablets were found both in water uptake and force development. The rate of water penetration may be related to tablet porosity and pore size for the formulations obtained by direct compression, double compression and compaction. However, the influence of simultaneously occuring phenomena, such as dissolution and/or pore widening, must be taken into account. In the case of wet granulation the water penetration rate is lower than expected on the basis of tablet porosity, due to the presence of the binder. The variability of the water penetration rate is related to the variability of mean pore diameter. As expected, the kinetics of force development is related to the kinetics of water uptake. Water penetration and force development studies proved useful to elucidate the microstructure of the tablets and to understand the interactions between water and polymeric chains: these interactions may in part explain the release pattern that is observed during dissolution tests.