The development of matrix tablets for diclofenac sodium based on an empirical in vitro and in vivo correlation

Different dissolution media were tested using Voltaren SR® as a model dosage form to develop an in vitro/in vivo correlation for diclofenac sodium. An empirical correlation between the cumulated amount of in vitro dissolution (%) and cumulated AUC (%) was constructed by selecting an appropriate time scale. Dissolution in a water medium for 1 h, followed with simulated intestinal fluid seemed to give better correlation with the AUC in vivo. This approach was tested with four matrix tablets based on hydroxypropylmethylcellulose (HPMC) of varying grades of viscosity and at different ratios. The closeness between in vitro dissolution profile and cumulated AUC change was conclusively demonstrated for these four matrix tablets. Based on this result, a product named Clofen SR® was then designed and was tested in vivo to compare its relative bioavailability with that of Voltaren SR®. The results demonstrated a similar extent of absorption in terms of AUC for Clofen SR® as for Voltaren SR®. However, the fluctuation in plasma concentration was smaller for Clofen SR® than for Voltaren SR® at steady state based on the three pharmacokinetic parameters of C((max)(ss)), C((min)(ss)), and Fluctuation((ss)). It is concluded that this empirical correlation may be able to predict the relative extent of absorption, but fails to indicate the possible erratic concentration change of diclofenac sodium in the plasma.