(M1030-09-51) Development of 3D Printed Oral Disintegrating Tablets of Oxcarbazepine Using Co-Processed Excipient

Purpose: Application of oral disintegrating tablets (ODTs) for central nervous system (CNS) diseases have gained significant attention to address patient compliance issues. Manufacturing of ODTs using 3-dimensional printing (3DP) technology has the unique advantage of producing highly porous structures. 3DP of ODTs involves additive manufacturing which assembles the tablet layer by layer. Among additive manufacturing techniques, binder jetting is the preferred technique for production of high dose ODTs by spreading the powder blend in a layer-by-layer manner followed by jetting of binder solution over the selected region. In the current study we evaluated the manufacturing of a high dose ODT of oxcarbazepine utilizing 3DP with Ludiflash® as co-processed excipient. Oxcarbazepine, an anticonvulsant drug, was selected for this study to evaluate the feasibility of manufacturing high dose ODT formulations for the treatment of CNS disorders.

Methods: Major steps involved in the manufacture of Oxcarbazepine ODT included print fluid preparation, powder blending and tablet formation using 3DP.  The print fluid was prepared by mixing povidone, glycerin, polysorbate 20 in isopropyl alcohol and water using impellers used for low viscosity fluids. Powder blends were prepared by mixing Ludiflash® and oxcarbazepine in 1:1 ratio using a Maxiblend® blender at 16 rpm for 10 minutes. ODTs were manufactured on a build plate through repetitive application of powder layers and printing fluid. The print fluid jetting was performed using a piezoelectric print head at an established waveform and voltage. After processing, tablets were dried in an oven at 60 °C followed by removal of excess powder. Binder fluid level and roller speed were optimized during this study. Tablets were characterized for weight, hardness, thickness, disintegration and dissolution using USP apparatus II.

Results: 3DP process was optimized for the blend by adjusting the number of powder layers, print fluid quantity and roller speed which resulted in acceptable tablets without any shifting. ODTs were printed at constant track speed. Printer output was 65 - 85 ng/drop. The powder bed layer height was adjusted to improve the tablet hardness from 3N to 9N. ODT target weight was achieved by adjusting print fluid spray amount and adjusting the layer thickness. The optimized process parameters resulted in ODTs with an average weight of 641± 7.3 mg. Average tablets thickness and hardness were 5.15 mm and 9.4 N, respectively. ODT disintegration time was 15 seconds for the tablets produced through the optimized parameters.

Conclusion: High dose ODTs were manufactured by 3DP using Ludiflash® as co-processed excipient. The 3DP process parameters were optimized to manufacture oxcarbazepine ODTs with acceptable physical characteristics. 3DP of high dose formulations using co-processed ODT excipients will enable faster evaluation of blend compositions. This research suggests that 3DP technology can be explored for the development of ODTs for other active pharmaceutical ingredients using co-processed excipients.

3D printed ODT of oxcarbazepine using co-processed excipient