Formulation design and optimization of fast disintegrating Lorazepam tablets by effervescent method.

摘要

Fast disintegrating tablets of lorazepam were prepared by effervescent method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and mixture of sodium bicarbonate, citric acid and tartaric acid (effervescent material) on in vitro dispersion time. Crospovidone (2-8% w/w) was used as superdisintegrant and mixture of sodium bicarbonate, citric acid and tartaric acid (6-18% w/w) was used 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 13 s); the formulation containing 8% w/w crospovidone and 18% w/w mixture of sodium bicarbonate, citric acid and tartaric acid was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables (concentrations of crospovidone and effervescent material) 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 marketed tablet for drug release profiles. This formulation showed nearly eleven-fold faster drug release (t(50%) 2.8 min) compared to the conventional commercial tablet formulation (t(50%) >30 min). Short-term stability studies on the formulation indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).