3D printing of extended-release tablets of theophylline using hydroxypropyl methylcellulose (HPMC) hydrogels.

Abstract

An extrusion based 3D printer was used to prepare the semi-solid tablets with different drug loading dosages (75, 100, 125mg) under ambient temperature. The active pharmaceutical ingredient, theophylline, was uploaded within the hydrogels prepared of hydroxypropyl methylcellulose (HPMC) K4M or E4M. The HPMC concentrations were adjusted to different levels (10 and 12% w/w) to fulfill the requirements for 3D printing. Rheological and textural properties, as well as release profiles, were significantly affected by the type and concentration of excipient regardless of theophylline doses used. The printing material should exhibit shear-thinning behavior, keeping yield stress less than 4000Pa and a loss factor (tanδ=G''/G') between 0.2 and 0.7, especially for 3D printing purposes using the current platform. The SEM images demonstrated that the hydrogel matrix exhibited a porous structure, which had the potential to encapsulate the theophylline clusters within its microstructure. The in vitro dissolution test showed that the release of all tablets was extended over 12h, and the calculation of drug release kinetic models revealed that the 3D printed HPMC matrices release the theophylline by diffusion and erosion mechanisms. The excipient HPMC K4M 12% w/w hydrogel was optimal to load the theophylline with flexible dosage combinations due to the great extrudability and shape retention ability. The exploration of rheological properties was investigated in this study, and the results revealed that it is a feasible method to predict the SSE 3D printability and quality of hydrogel-API blend materials for the drug delivery system.