Formulation and pharmacokinetics of multi-layered matrix tablets: Biphasic delivery of diclofenac

Abstract

The rapid availability of the drug at the site of action followed by maintaining its effect for a long period of time is of great clinical importance. Thus, the purpose of the present study was to prepare and evaluate multi-layered matrix tablets of diclofenac using Eudragit RL/RS blend to achieve both immediate and sustained therapeutic effects. Diclofenac potassium (25 mg) was incorporated in an outer immediate release layer to provide immediate pain relief whereas diclofenac sodium (75 mg) was incorporated in the inner core to provide extended drug release. Wet granulation was employed to prepare the inner core of the tablets that were further layered with an immediate release drug layer in the perforated pan coater. The in-vitro and in-vivo performance of the developed formulation was compared with the marketed products Voltaren® SR 75 mg and Cataflam® 25 mg. The in-vitro drug release of the prepared formulation showed similarity (f2 = 66.19) to the marketed product. The pharmacokinetic study showed no significant difference (p > 0.05) in AUC0-24 and Cmax between the test and reference formulations. The AUC0-24 values were 105.36 ± 83.3 and 92.87 ± 55.53 μg h/ml whereas the Cmax values were 11.25 ± 6.87 and 12.97 ± 8.45 μg/ml, for the test and reference, respectively. The multi-layered tablets were proved to be bioequivalent with the commercially available tablets and were in agreement with the observed in-vitro drug release results. Stable physical characteristics and drug release profiles were observed in both long term and accelerated conditions stability studies.

Keywords

• Diclofenac
• Matrix
• Pharmacokinetic
• Bi-phasic release
• In-vivo
• Multi-layered tablets