(W1130-12-68) High Drug Loading Sustained-Release Metformin HCl Tablets: Hydroxypropyl Methylcellulose (HPMC) Based Semi-solid Extrusion 3D Printing

Purpose: Commercially available metformin HCl (MET) sustained-release tablets are inconvenient to take due to the large size of the tablets due to large amounts of excipients. The purpose of this study was to develop sustained-release high drug loading MET tablets using an extrusion-based 3D printer from a pre-mixed HPMC based paste formulation.

Methods: Hydroxypropyl methylcellulose (HPMC)-loaded hydroalcoholic gel was prepared to make a paste for a semi-solid extrusion 3D printer. Thereafter, the MET fine powder and microcrystalline cellulose (MCC) were mixed at prepared HPMC gel solution. The physical properties of the produced paste were evaluated to obtain an optimal paste having properties suitable for extrusion through a printer head. MET 3D printed tablets were fabricated as an oval-shape having a size of 19.1mm length × 9.3mm width × 6.5mm height same as the commercial product. Finally, the similarity was evaluated through a dissolution test using the manufactured 3D printed tablet and a commercial product. In addition, physicochemical characteristics were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) assessments.

Results: A paste suitable for the semi-solid extrusion 3D printer was produced through the paste optimization process. Although some shrinkage of the tablet was found during the drying process after 3D printing, conditions were found to minimize this, and as a result, the high drug loading MET tablets were successfully manufactured. In this study, two types of HPMC (4,000 and 100,000cps) were used to compare the effect of HPMC grade on dissolution of 3D printed tablets. As a result, as the viscosity of HPMC increased, a delayed dissolution pattern was obtained, and a formulation having dissolution similar to that of a commercial product could be prepared.

Conclusion: Some medicines are difficult to reduce the size of the tablet because of the excipients absolutely necessary for sustained release purpose. In this study, we successfully fabricated MET-loaded 3D-printed tablets having a similar dissolution pattern and high drug content compared to commercial products. This technology could be used as a way to make high drug loading tablets via semi-solid extrusion 3D printing.

Figure 1. Images of metformin HCl 3D printed tablets; HPMC 4000cps (5%, w/w), HPMC 100,000cps (5%, w/w).



Figure 2. Dissolution profile of metformin HCl 3D printed tablets; F1 is HPMC 4000cps (5%, w/w), F2 is HPMC 100,000cps (5%, w/w).