Development of methylcellulose‐based sustained‐release dosage by semisolid extrusion additive manufacturing in drug delivery system

Abstract

The objective of this study is to fabricate customized dosage forms using extrusionbased 3D printing for the sustained delivery of theophylline. The therapeutic paste was prepared by combining various doses of theophylline (0, 75, 100, and 125 mg) with different concentrations of methylcellulose (MC) A4M (8, 10, and 12%). The paste was then 3D printed into semisolid tablets under optimized printing conditions. The rheological properties of printing pastes were related to the 3D printability. Our results indicated that to be 3D printed using the current platform, the storage modulus (G 0) of the printing paste should be higher than the loss modulus (G 00) during the frequency sweep (0.1-600 rad/s), and the tan δ should fall in the range of 0.25-0.27 at 0.63 rad/s. The printed tablets formulated with 10% MC showed the highest overall quality, considering the aspects of resolution, texture, and shape retention regardless of the dosage. The scanning electron microscopy images indicated that the cross-linked structure of MC A4M formed the microscale porous microstructure, which has the potential to embed the theophylline, thus delayed the release through the barrier effect. The in vitro dissolution test revealed that the 3D printed tablets exhibited a sustained release during the first 12 hr. The findings in this study will support the development of customized, personalized medicine with improved efficacy.

The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines

“…Semi-solid extrusion of tablets containing theophylline at ambient temperature after processing at 70 °C [ 63 ]…”

Development and characterization of 3D bioprintable and mechanically reinforced hydrogel based on gellan gum/methylcellulose/cellulose nanocrystals

“…As observed at 25 C, in the presence of salts, the difference between G 0 and G 00 was higher compared to that without salts (1GG/4MC and 1GG/4MC/4CNC), reflecting stronger mechanical strength of both 1GG/4MC/4CNC/0.022CaCl 2 and 1GG/ 4MC/4CNC/0.075KCl as previously described. 79…”

Solvent-free temperature-facilitated direct extrusion 3D printing for pharmaceuticals

“…In addition, it avoids a high processing temperature, thus poses an attractive alternative to FDM. However, the starting materials and their mixing ratios should be carefully considered to meet required strict rheological properties that allows a smooth, reproducible and efficient extrusion which can solidify following 3D printing completion (12,13). In most cases, solvent (often water) is used to facilitate material flow through reducing the viscosity of the mixture (14).…”