3D printing of cellulose derivatives based-biogel matrices as the drug delivery system and support structure

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Cheng, Yiliang
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Xiaolei Shi
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Food Science and Human Nutrition

Within the last decade, three-dimensional (3D) printing has attracted an unprecedented interest as a promising technology due to its high flexibility and cost-effectiveness. The hydrogels and colloids formed by biopolymers such as cellulose derivatives have been considered as the most critical materials for the development of 3D printing technology because of their biodegradability and biocompatibility. In this work, two types of cellulose derivatives, hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC), were selected as the potential materials to assess their printability by using semi-solid extrusion (SSE) based 3D printer. The HPMC and MC based hydrogels showed a shear-thinning behavior, which is desirable for the extrusion-based 3D printing. Since HPMC and MC are also widely used in the conventional pharmaceutical industry, the feasibility of using an SSE-based 3D printer to fabricate cellulose derivative-based tablets was also investigated. The 3D printed tablets contained two solid ingredients, cellulose derivatives as the excipient and theophylline as the active pharmaceutical ingredient (API). The therapeutic paste was prepared by combining various doses of theophylline (0, 75, 100, 125mg) with different concentrations of excipients (8, 10, and 12%). The paste was then 3D printed into semi-solid tablets under optimized printing conditions under ambient temperature. The concentration and type of excipient played predominate roles in determining the 3D printing potential, which was related to the rheological and textural properties. The results of apparent viscosity, yield stress, storage modulus, and hardness showed a significant increase with the increase in excipient concentration. For tablets with different excipients, the MC A4M 12% (w/w) based tablets showed the best printing quality and shape retention ability, followed by HPMC K4M 12% (w/w) based tablets. The tan δ values of these tablets with optimal printability fell in the range between 0.2 and 0.7, which indicated the solid-like property. The increased concentration of excipient also significantly increased the magnitude of storage modulus. The results of flow behavior and oscillation sweep tests could be used to predict the printability of potential materials for 3D printing purposes using the current platform.

The SEM images demonstrated that the cross-linked hydrogel matrix exhibited a porous three-dimensional structure, which had the potential to encapsulate the theophylline particles within its microstructure. The in vitro dissolution test showed that the release of all tablets regardless of the excipient type was extended over 12 hours. After the dissolution test, the matrices of MC A4M based tablets were still kept in their original structures, which indicated that MC A4M formed the porous microstructure to delay the release through the barrier effect. The release profiles of all these cellulose derivative-based tablets were well fitted into first-order and Korsmeyer-Peppas models, which showed non-Fickian diffusion. Besides, 3D printed cellulose derivative-based biogel matrices transport the theophylline by both diffusion and erosion mechanisms. The findings in these studies would support the development of patient-tailored and extended-release tablets by using the SSE based 3D printing technology.

Also, the 3D printable characteristics of HPMC K4M hydrogel showed the potential to fabricate a biodegradable support structure in the manufacturing industry. Similar to the 3D printed tablets, the printed geometries with HPMC K4M 12% (w/w) concentration also showed the optimal 3D printing quality and mechanical strength after the printing process. This material was feasible to be 3D printed into geometries with different infill density (100%, 75%, and 50%) and different patterns (rectilinear and Hilbert curve). Since HPMC is produced from renewable resources, the cellulose derivative polymers could be used to replace the petroleum-based materials in the 3D printing application with future improvement.

Sat Aug 01 00:00:00 UTC 2020