Box Behnken design in the optimization of two disintegrants and a sublimating agent in the formulation of fast disintegrating tablets of diclofenac

Abstract

The aim of the study was to formulate fast disintegrating tablets of diclofenac with a combination of disintegrants and sublimating agent, and to optimize the concentrations of the disintegrants and the sublimating agent for a faster tablet disintegration. A Box Behnken experimental design model was used to generate 17 possible combinations of two disintegrants (maize starch BP and croscarmellose sodium) and a sublimating agent (camphor). Using these combinations, 17 batches of diclofenac sodium tablets were prepared by direct compression and subjected to disintegration and crushing strength tests in order to select optimal batches. Bulk formulation of granules and tablets of the optimal batches was carried out and evaluated for granule flow properties (bulk and tapped densities, angle of repose, Hausner’s ratio and Carr’s index) and post compression parameters (weight uniformity, tablet dimensions, crushing strength, friability, disintegration and dissolution). Drug-excipient interaction studies were also carried out using DSC and FTIR. Results from the granule analysis of the optimal batches indicated free flowing granules. The disintegration times and crushing strengths of the tablets were < 3 min and > 4 kp respectively and they corresponded with the values obtained from the experimental design model. All the batches of tablets released up to 95 % of their drug content within 30 min. Drug-excipient compatibility study revealed no interaction between diclofenac sodium and the excipients used. Fast disintegrating tablets of diclofenac were thus successfully formulated using a Box Behnken design in the combination of two disintegrants and a sublimating agent. Batch B14 formulation with a disintegration time of 26.55 seconds and a crushing strength of 4.25 kp was the most superior of the optimized batches.

Keywords: diclofenac, disintegrants, camphor, Box-Behnken, optimization, tablets