Development Optimization and Evaluation of Stable Oral Suspension for Adjunctive Treatment of Epilepsy In Pediatric Patients

Abstract

Drug X, is a non competitive antagonist falls under BCS class-II antiepileptic drug used to treat partial onset and generalised tonic-clonic seizure by inhibiting AMPA glutamate receptor. Drug X recommended starting dose is 1mg/ml for children weighing less than 20kg and 2mg/ml for children weighing >30 kg as well as for adult. Thus conventional dosage form that have dose of 2 mg upto 12 mg in tablet form, a pediatric patient will requires a low dose formulation respectively to consume each day. A oral suspension (0.5 mg/ml) will offer easiness and convenience in administration. Formulation of oral suspension was carried out by direct dispersion method. Poloxamer 188, simethicone emulsion, avicel rc 591, citric acid (anhydrous), sodium benzoate, neosorb 70/70B were used to formulate oral suspension. During formulation studies, suspension was been evaluated for various parameters like redispersibility (95), % assay (103.4%), viscosity (163cps), pH (4.53), weight per ml (1.015gm/ml), and % drug release. The experimental studies revealed that the poloxamer 188 as a surface-active agent and avicel RC591 as suspending agent played an important role to obtain desired product characteristics. An increase in the concentration of the avicel was able to reduce the sedimentation rate; whereas homogenization time had helped to reduce the particle size, uniform mixing and reproducible drug release rates. Stability study of prepared oral suspension was done at 40ºC/75%RH for optimized trial batches for 30 days and it was found within specified limits. F2 similarity value (87) shows that optimized trial batch (T8) was found equivalent with drug release profile in comparison to its reference listed drug product, having drug X (0.5mg/ml) in oral suspension.