Category: Formulation and Quality
Purpose: The objective of this study is to develop a new way of fabricating a controlled release tablet using Hot melt extrusion (HME) and 3D printing technology. The tablet should first be able to have a burst release which would be followed by a sustained released designed to keep the therapeutic window open longer. Then a mathematical model to accurately predict the rates of release by correlating the geometry of the 3D printed tablets with their drug release rates to understand the mechanism of drug release from the printed tablet was developed.
Methods: Ketoprofen, a nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects, was mixed with HPMC K4M, HPMC- AS HG and HPC-LF to combine different core and shell formulations (Table. 1). Filaments were prepared using a Thermo Fisher Scientific 11mm twin-screw co-rotating extruder. A customized fuse-deposition model (FDM) based Original Prusa i3 MK3S 3D printer was used to produce different densities tablets. The tablets were printed with a loose and porous shell, (20%, 30%, and 40% fill density) and tight and thick cores (40%, 50%, and 60% fill density) then combined together (Fig 1.). Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) analyses were performed to determine the thermal stability of Ketoprofen and polymer matrix. Photomicrographs were taken using a scanning electron microscopy (SEM) to improve the understanding of the internal structure of the tablets. Tablets hardness tests and geometry studies were also performed.In vitrodrug release studies were conducted using USP-II dissolution apparatus with phosphate buffer (pH 6.8). Higuchi model Ritger-Peppas model, Peppas-Sahlin model, first order, and zero order kinetics, models were studied helps us understand release mechanisms and optimize formulations .
Results: This study successfully fabricated solid-dispersion filaments with the API dissolved in a polymer matrix via HME technology and produced controlled release tablets with different 3D structures. DSC and TGA results showed the polymer matrix would be stable during HME and 3D printing process. SEM showed the difference of core and shell structure and the layer-by-layer printing feature. The 20% Shell and 40% core tablet had the best release rates in this study; it released faster and ensured that the drugs therapeutic window stayed open longer. The drug release successfully fits Ritger-Peppas model and from the Peppas-Sahlin model showed that the drug release diffusion methods may be dominated by Case Ⅱtransportation diffusion (skeletal erosion).
Conclusion: This research successfully combined 3D printing and HME to produced controlled release tablets with different densities. This research provides a foundation for the development of controlled release tablets using combined 3D printing and HME technology thus expanding the use of this emerging technology for the development of more complex pharmaceutical in the future.