3D printed capsule shells for personalized dosing of cyclosporine-loaded SNEDDS

Abstract

Cyclosporine (CsA) is a potent immunosuppressant agent that has been used since 1980 for the treatment of various autoimmune diseases and is extensively used to enhance the survival rate of patients and grafts following organ transplant surgeries. CsA is a poorly soluble drug with a narrow therapeutic window and inter-subject variability, which can lead to graft rejection, nephrotoxicity and other severe adverse effects. This study explores a novel method that combines solubility enhancement of CsA using SNEDDS formulation and personalized dosage delivery using 3D printing technology. The oil phase was chosen as a combination of caproyl 90 and octanoic acid while the Smix phase was chosen as a combination of cremophore El and PEG 400. The optimized liquid SNEDDS was solidified using PEG 6000. An FDM printer was used to print a capsular shell with an oval base that ascends to form a dome with an opening at the top. This opening is used to fill the molten CsA-loaded SNEDDS formulation using a pipette or syringe. The CsA-loaded SNEDDS formulation was characterized by FTIR, DSC and SEM/EDX. The in-vitro release of CsA showed complete release within sixty minutes and followed Korsmeyer-Peppas release kinetics. The drug release was not affected by either the shell opening size or the amount of the loaded formulation. This novel method is simple and straightforward for personalized dosage delivery of drug-loaded SNEDDS formulations.