Formulation, Optimization and in Vitro Evaluation of Rapid Disintegrating and Mucoadhesive Sublingual Tablets of Lorazepam

Abstract

Lorazepam a benzodiazepine drug is used as an antianxiety, sedative, hypnotic, and anticonvulsant drug. Bypassing the enterohepatic recirculation and first-pass metabolism of lorazepam by sublingual delivery of this drug may accelerate the onset of its action. The objective of this study was the formulation, optimization and in vitro characterization of mucoadhesive sublingual tablets of lorazepam. To optimize the formulation of the mucoadhesive sublingual tablets of lorazepam seven variables including: disintegrating agent type (Primojel or Kollidone), filler Silicified microcrystalline cellulose (SMCC) or Avicel PH 101, carrier powder (mannitol or lactose), disintegrating agent content (5 or 10%), lubricant type (Mg-stearate or Aerosil), drug content (1 or 2 mg) and mixing time (12 or 24 h) were studied by the Taghuchi design and nine different formulations were prepared. The tablets were tested for their thickness, hardness, weight variation, drug content uniformity, assay, porosity, disintegration time, bioadhesion tensile strength and dissolution efficiency and the effect of different studied formulation parameters were studied on their properties. The formulation of tablets was optimized considering their dissolution efficiency within 10 minutes (DE10%). The optimum formulation obtained from 2 mg of the drug, 1.2 mg Mg-stearate, 6 mg of Primojel, 20.8 mg of Avicel, 90 mg of mannitol which was mixed for 12 hours with the drug. This tablet with the DE10% of 81.30 +/- 2.50%, bioadhesion of 34.15 +/- 0.15%, and disintegration time of about 14 sec seems promising as a rapid disintegrating and mucoadhesive sublingual tablet for lorazepam.