3D printed pH-responsive tablets containing N-acetylglucosamine-loaded methylcellulose hydrogel for colon drug delivery applications

The pH-responsive drug release approach in combination with three-dimensional (3D) printing for colon-specific oral drug administration can address the limitations of current treatments such as orally administered solid tablets. Such existing treatments fail to effectively deliver the right drug dosage to the colon. In order to achieve targeted drug release profiles, this work aimed at designing and producing 3D printed tablet shells using Eudragit® FS100 and polylactic acid (PLA) where the core was filled with 100 µL of N-acetylglucosamine (GlcNAc)-loaded methyl cellulose (MC) hydrogel. To meet the requirements of such tablets, the effects of polymer blending ratios and MC concentrations on physical, thermal, and material properties of various components of the tablets and most importantly in vitro drug release kinetics were investigated.

The tablets with 80/20 weight percentage of Eudragit® FS100/PLA and the drug-loaded hydrogel with 30 mg/ml GlcNAc and 3% w/v MC showed the most promising results having the best printability, processability, and drug release kinetics besides being non-cytotoxic. Manufacturing of these tablets will be the first milestone in shifting from the conventional “one size fits all” approach to personalized medicine where different dosages and various combinations of drugs can be effectively delivered to the inflammation site.

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Materials

GlcNAc, dithiothreitol, (NH4)Fe(SO4)2·12H2O, sodium hydroxide (NaOH), and sulfamic acid was purchased from Carl Roth (Germany). Eudragit® FS100 polymer was kindly gifted from Evonik (Germany). Luminy® PLA LX930 was purchased from Total Corbion PLA (Thailand) Ltd. MC was purchased from Sigma–Aldrich (Germany) and used as a hydrogel structure. Hydrochloric acid (37%), and Phosphate buffered saline (PBS) tablets were purchased from VWR Chemicals, LLC (USA) and Thermo Fisher Scientific (USA), respectively. Dialysis tubing cellulose membrane (molecular weight cut-off=14,000), dimethyl sulfoxide (DMSO), 3-methyl-2-benzothiazolinonhydrazon, and cell proliferation kit II (XTT) were purchased from Sigma–Aldrich (Germany). Polymerase chain reaction (PCR) plates, Gibco™ Dulbecco’s modified Eagle’s medium (DMEM), and fetal calf serum (FCS) were purchased from Thermo Fisher Scientific (USA). Finally, all materials were used without further purification.

Maryam Asadi, Zeinab Salehi, Mohammad Akrami, Mohammadreza Hosseinpour, Stefan Jockenhövel, Samaneh Ghazanfari, 3D printed pH-responsive tablets containing N-acetylglucosamine-loaded methylcellulose hydrogel for colon drug delivery applications, International Journal of Pharmaceutics, 2023, 123366, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123366.

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