Tailored Drug Release for Arthritis: 3D Printed Paracetamol Using HPMC Filaments for Elderly Patients

Abstract

Three-dimensional printing (3DP), initially developed for non-medical applications and once considered futuristic, has recently gained traction in pharmaceutical manufacturing. However, existing materials used in drug printing, such as inks and filaments, face significant challenges, including limited biocompatibility, poor extrudability, low drug loading capacity, and instability. In this study, we developed a filament using a single pharmaceutical polymer, hydroxypropyl methylcellulose (HPMC), without any additives. This filament is versatile and can be customized through computational design to produce tablets with tailored release and absorption profiles.

We utilized HPMC and paracetamol to create drug-loaded filaments, which were then evaluated for their thermal and crystalline properties and cytotoxicity. The focus of this research was to investigate the impact of layer thickness during 3D printing on drug release characteristics. By alternating the thickness of the printed layers, we produced various tablet designs and analyzed their drug release behaviors. We found that varying the layer thickness significantly affected the release rate of paracetamol, with thicker layers generally resulting in slower drug release due to reduced surface area exposure to the dissolution medium.

Stability tests demonstrated that both paracetamol and HPMC remained stable at the temperatures used for extrusion and printing, with a drug loading of 10% (w/w). The drug release rate was strongly influenced by both the infill density and layer thickness, with higher infill densities and thicker layers leading to a notable decrease in the percentage of drug released. Tablets with alternating thicknesses and layers of drug-free and drug-loaded filaments exhibited delayed and intermittent drug release, depending on the interaction of drug-loaded layers with the dissolution medium.

Furthermore, the drug release profiles observed in vitro were consistent with the absorption patterns seen in cellular studies, showing immediate, extended, delayed, and episodic drug absorption in the gastrointestinal tract. This research highlights the potential of using HPMC-based filaments without additives for 3D printing personalized drug delivery systems. By optimizing parameters such as layer thickness and infill density, 3DP offers a promising approach to creating customized therapeutic solutions, particularly for elderly patients with arthritis.