Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms

Abstract

Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation

“…This dense network acts as a robust barrier to drug diffusion, resulting in a slower drug release rate from the dosage form. Moreover, the higher molecular weight of the polymer correlates with increased gel viscosity upon contact with dissolution media, further retarding drug release over an extended period [ 28 , 46 , 47 ].…”

“…The polymer grade is a crucial factor in the quality control and drug release profiles of pharmaceutical formulations [ 27 , 28 , 29 , 30 , 31 ]. Hartzke et al demonstrated this in their development of 3D-printed CR tablets using various grades of hydroxyethyl cellulose (HEC), specifically 90 kDa, 300 kDa, 720 kDa, and 1000 kDa, showing significant variations in dissolution release profiles [ 28 ].…”

“…The polymer grade is a crucial factor in the quality control and drug release profiles of pharmaceutical formulations [ 27 , 28 , 29 , 30 , 31 ]. Hartzke et al demonstrated this in their development of 3D-printed CR tablets using various grades of hydroxyethyl cellulose (HEC), specifically 90 kDa, 300 kDa, 720 kDa, and 1000 kDa, showing significant variations in dissolution release profiles [ 28 ]. Similarly, research on different grades of polyethylene glycol (PEG)—PEG 4000, 6000, and 20,000—revealed an influence on the mechanical properties of formulations due to melting point differences [ 30 ].…”

Excipients in Pharmaceutical Additive Manufacturing: A Comprehensive Exploration of Polymeric Material Selection for Enhanced 3D Printing

“…Compared to HPC and EC, and even HPMC, the poor thermoplastic behavior of HEC might explain the lack of available studies for HEC in thermal manufacturing processes, such as FDM-based 3D printing. Hartzke et al [ 57 ] evaluated the processability of different grades of HECs in FDM printing and figured out that extrusion of HEC alone was not possible. To overcome this process limitation, the authors mixed HEC (75% w / w ) with thermoplastic HPC (20% w / w ) to improve the overall thermoplastic behavior of the mixture.…”

“…This demonstrates the importance of blending polymers with different properties to facilitate processability based on the requirements of the AM process. The authors concluded that low-viscosity HEC of grade 250 L with a low MW was the most suitable, resulting in sufficient feedability and printability of the filament and the high breaking force of the fabricated tablets [ 57 ]. Fina et al [ 58 ] included high-MW-grade HEC 250H as a matrix-forming suspending agent in a formulation comprised of HPC, polyethylenoxide (PEO), and mannitol.…”