Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride

Abstract

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl₂ at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Keywords: alginate ionotropic gelation; floating DDS; semi-solid extrusion 3D printing.

Figure 1

Results from rotational test (a) and amplitude sweep test (b) for crosslinking and alginate inks.

Figure 2

Photo of DDS immediately after printing.

Figure 3

FT-IR spectrum of RBZ raw material, dried film obtained from RBZ-HEC gel, drug-free DDS and RBZ loaded DDS; RBZ structure, with schematic representation of the chemical bonds, was reported to allow for data analysis.

Figure 4

Thermographs of RBZ raw material (black line), drug-free DDS (green line), and RBZ-loaded DDS (blue line).

Figure 5

SEM acquisition of: (a) external view of single layer after drying; (b) a cross-section view of DDS; (c) a longitudinal-section view of DDS.

Figure 6

Cross-section SEM acquisition of (a) dried DDS0.10_5; (b) dried DDS0.05_5; (c) DDS0.10_5 after dissolution and re-drying; (d) and DDS0.05_5 after dissolution and re-drying.

Figure 7

Load-crosshead curve of DDS0.05_R5 (green line) and DDS 0.10_R5 (red line).

Figure 8

Dissolution profile of (●) DDS0.05_R5 and (■) DDS0.10_R5 (the x-axis is interrupted at 8 h and re-plotted at 22 h for better data display). The red arrow indicates the time interval in which the sinking of DDS0.05_R5 occurs.