Engineering immediate release tablets with customized design and drug combination via fused deposition modelling 3d printing

Abstract

In respect of personalised doses, fused deposition modelling 3D printing delivers a viable alternative to the mass manufacture of pharmaceuticals. Its advantages draw from low-cost, convenient use and flexible bespoke dosages. However, few polymers are compatible with the fused deposition modelling 3D printing of pharmaceuticals out of which very little is for immediate-release. The aim of this work was to investigate the feasibility of manufacturing immediate-release dosage forms with customised designs and drug combinations, using fused deposition modelling 3D Printing.

Five drugs with different physicochemical properties were investigated to ascertain the practicality of using an immediate release methacrylate polymer (Eudragit EPO) and thermally stable filler (tribasic calcium phosphate). Filaments were optimised against the constraints of thermal stability, flexibility, rheological properties and compatibility with a bench top 3D printer. For the drugs investigated, the manufacture of ready-to-use mechanically stable tablets with immediate release properties was successful. In combining thermally stable pharmaceutically approved polymers and fillers, a viable production method was demonstrated for the on-demand manufacture of customised dosages.

Although fixed-dose combinations are marketed, their inherently rigid nature does not allow the titration of every component for individual patient needs, which leads to non-compliance by increasing the number of tablets taken by the patient. Using a dual 3D printer, and enalapril maleate and hydrochlorothiazide loaded filaments produced via hot melt extrusion; a range of flexible dose combinations of two anti- hypertensive drugs in a single bilayer tablet was produced by altering individual drug’s layer thickness. Across all tablet sets, the methacrylate matrix delivered comparable in vitro drug release profiles. This dynamic dosing system retained the advantages of fixed-dose combinations while providing superior flexibility in the dosing range, thereby offering an optimal clinical solution to hypertension. A large amount of polymer that is necessary for fused deposition modelling 3D tablet printing retards drug release through erosion and diffusion. In addressing that problem, we utilise a novel design of caplets with perforating square channels, which accelerate drug release from the increased surface area/volume ratio.

To ascertain their stability and shelf life, filaments were stored as pre-products for six months, both at room temperature and in a refrigerator. Three polymers were used with a high melting-point drug theophylline. For Eudragit RL and Eudragit EPO the results were successful; but, by its hygroscopic nature, the experiment confirms that hydroxypropyl cellulose SSL cannot be stored for prolonged periods. Provided that the clinical work is carried out, this work has paved the way to manufacture individualised doses and bespoke designs of dosage forms in an economical way.