Formulation Design and Optimization of Fast Dissolving Effervescent Tablets of Clonazepam

Abstract

A B S T R A C T Fast dissolving tablets of clonazepam were prepared by effervescent method with a view to enhance patient compliance. A 3² full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and 1:1 mixture of sodium bicarbonate and anhydrous citric acid. Crospovidone (2-8% w/w) was used as superdisintegrant and mixture of sodium bicarbonate and anhydrous citric acid (16-48% w/w) as effervescent material, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 10 sec); the formulation containing 8% w/w crospovidone and 48% w/w effervescent material was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer),accelerated stability (at 40oC/75% relative humidity for 6 months) and drug-excipient interaction (FT-IR analysis). Surface response plots are presented to graphically represent the effect of independent variables on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design check point formulations. The optimized tablet formulation was compared with conventional commercial tablet for drug release profiles. This formulation showed nearly nine-fold faster drug release (t 1.9 min) compared to the conventional commercial 50%