Fabrication of high drug loading levetiracetam tablets using semi-solid extrusion 3D printing

Abstract

The present study was designed to appraise the superiority of semi-solid extrusion 3D printing technology in the fabrication of high drug loading (96% w/w) levetiracetam tablets. The tablets were developed as three geometrical shapes (cylinder, oval and torus) and prepared with hydroxypropyl cellulose (HPC-M) as a binder and croscarmellose sodium (CCMC-Na) as disintegrant. The printed high drug loading tablets had satisfactory physical performance and mechanical properties. SEM, DSC and XRPD, as well as FTIR, showed that the physical forms of levetiracetam in the tablets was not affected in the printing process, and there was no detectable interaction between the levetiracetam and the excipients. The lattice architecture was designed and modified by control of the lattice cell size to accelerate the drug release rate. As a result, a fast drug release from the high drug loading levetiracetam tablets that showed more than 85% drug release within 15 min was obtained for all geometrically shaped tablets of different infill percentages, except for the 100% infill cylinder tablets. The optimum (greatest) drug release (97.45% within 2 min) was achieved in the torus tablets with 50% infill (the cell size was 1.0 mm). The potential of manufacturing high drug loading levetiracetam tablets was thus demonstrated, and the effectiveness of 3D extrusion printing in accelerating the drug release rate by control of the lattice cell size was assessed.