Improving the dissolution of a water-insoluble orphan drug through a fused deposition modelling 3-Dimensional printing technology approach

Lennox-Gastaut Syndrome (LGS) is a rare form of childhood epilepsy. Rufinamide is an orphan drug indicated for the treatment of LGS. Three-Dimensional Printing (3DP) is a process in which solid objects are created based on a digital file by adding materials layer by layer. Fused deposition modelling (FDM) is a 3DP technique with the advantages of solid dispersion systems and the ability to use various pharmaceutical excipients in small scales, which makes this technology favorable for the production of orphan drugs. Rufinamide is a water-insoluble lipophilic compound which can exist in different polymorphic forms. The therapeutic dose is 3200 mg/day, at which rufinamide exhibits nonlinear pharmacokinetics, which may be attributed to its limited solubility. The main purpose of this paper is to improve the dissolution of rufinamide through the use of 3DP technology. For this purpose, optimum 3DP tablets were developed based on 3DP manufacturability and dissolution behaviors. The findings suggest that a mixture of hydroxypropyl methylcellulose (HPMC), Soluplus (R), Kollidon (R) VA64, Gelucire (R) 48/16 and Triacetin are suitable excipients for FDM-3DP technology that can improve the dissolution of rufinamide. The optimum 3DP tablet shows significantly higher dissolution than Inovelon (R) at the therapeutic dose due to its improved wdissolution.