Formulation design and optimization of fast dissolving clonazepam tablets

Sarasija Suresh,Pv Swamy,Sb Shirsand

doi:10.4103/0250-474x.58189

Abstract

Fast dissolving tablets of clonazepam were prepared by direct compression 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 microcrystalline cellulose. Crospovidone (2-8% w/w) was used as superdisintegrant and microcrystalline cellulose (20-40% w/w) was used as diluent, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 16 s); the formulation containing 2% w/w crospovidone and 40% w/w microcrystalline cellulose was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer). Short-term stability (at 40°/75% relative humidity for 3 mo) and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables on the invitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design checkpoints. The optimized tablet formulation was compared with conventional commercial tablet formulation for drug release profiles. This formulation showed nearly five-fold faster drug release (t50% 3.5 min) compared to the conventional commercial tablet formulation (t50% 16.4 min). Short-term stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).

Highlights

Fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance
Recent advances in novel drug delivery systems (NDDS) aim to enhance safety and efÞcacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance i.e., one, which will rapidly disintegrate in the mouth without need of water
In vitro dissolution studies on the promising formulation (F3), the control (F0) and commercial conventional tablet formulation (CF) were carried out in pH 6.8 phosphate buffer and the various dissolution parameter values, viz., percent drug dissolved in 5 min (D5), 10 min (D10), dissolution efÞciency[13] at 10 min (DE10min), t50%, t70% and t90% are shown in Table 3 and the dissolution proÞles depicted in Þg. 1

Summary

Formulation Design and Optimization of Fast Dissolving Clonazepam Tablets

Fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance. Based on in vitro dispersion time (approximately 16 s); the formulation containing 2% w/w crospovidone and 40% w/w microcrystalline cellulose was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer). Short-term stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P

Directly compressible mannitol

Findings

Formulation code