Development and characterization of fast dissolving sublingual films containing Midazolam

Abstract

Midazolam, a short-acting benzodiazepine derivative is an upcoming therapeutic agent in the treatment and management of status epilepticus in pediatric patients. This study aims to formulate and evaluate the fast dissolving sublingual films of Midazolam with an aim to enhance the poor oral bioavailability due to first-pass metabolism. Pullulan, a natural polysaccharide produced from starch by the fungus, Aureobasidium pullulans, was used as the polymer in the formulation of films. We prepared fast dissolving films by solvent casting technique. Seven formulations were prepared by varying the concentration of pullulan and the plasticizer, PEG 400. Biophysical tests confirmed that there was no interaction between the drug and polymer. The films were evaluated for various physical parameters and for drug content and drug release. The films exhibited an acceptable range from 96.51-100.2% for drug content. The drug release was in the range of 95.1- 99.7% in 30 minutes for seven formulations. In vivo pharmacodynamic studies on male wistar rats suggested a four-fold increase in efficacy of the formulation compared with intraperitoneal dose of Phenytoin sodium. Our results describe an effective sublingual formulation of Midazolam that has potential therapeutic application in epilepsy.