Formulation Development and In-Vitro Characterization of Oral Levetiracetam Microspheres

Abstract

The purpose of the present investigation was to prepare oral microspheres of levetiracetam with a view to reduce the frequency of dosing and to attain steady state drug levels in addition to masking the bitter taste and faint odor of drug. Levetiracetam is a second-generation antiepileptic agent useful in the treatment of partial onset and myoclonic seizures, which has short plasma half-life of 7 ± 1 hour in adults along with bitter taste and faint odor. Microspheres are suitable drug delivery system for such drug candidate. Microspheres were prepared by various methods like w/o/o double emulsion solvent diffusion and w/o/w double emulsion solvent evaporation technique. Preformulation studies were carried out to rule out any drug-polymer interactions by DSC technique. In the formulations prepared by w/o/o method, the drug entrapment efficiency ranged from 70.73% ± 2.96 to 94.20% ± 2.75, mean particle size ranged from 300µm ± 9.0 to 454µm ± 8.02 and percentage yield ranged from 66.00% ± 4.58 to 87.33% ± 2.08 whereas, formulations prepared by w/o/w method, the drug entrapment efficiency ranged from 40.90% ± 4.46 to 49.26% ± 1.10, mean particle size ranged from 353µm ± 9.01 to 373µm ± 4.50 and percentage yield ranged from 62.66% ± 4.04 to 76.33% ± 6.11. In the in vitro release studies initial burst release was observed from all the formulations. The most satisfactory formulation released drug for 24hours. SEM studies of the most satisfactory formulation showed that the microspheres were spherical and porous in nature. The data obtained from in vitro release showed highest correlation with Higuchi model and the drug release was found to be diffusion controlled.