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. 2023 Mar 10;15(3):900.
doi: 10.3390/pharmaceutics15030900.

Micro-Injection Moulding of PEO/PCL Blend-Based Matrices for Extended Oral Delivery of Fenbendazole

Gilberto S N Bezerra  1 , Gabriel G De Lima  1   2 , Declan M Colbert  1 , Elaine Halligan  1 , Joseph Geever  1 , Luke Geever  1
Affiliations

Micro-Injection Moulding of PEO/PCL Blend-Based Matrices for Extended Oral Delivery of Fenbendazole

Gilberto S N Bezerra et al. Pharmaceutics. .

Abstract

Fenbendazole (FBZ) is a broad-spectrum anthelmintic administered orally to ruminants; nevertheless, its poor water solubility has been the main limitation to reaching satisfactory and sustained levels at the site of the target parasites. Hence, the exploitation of hot-melt extrusion (HME) and micro-injection moulding (µIM) for the manufacturing of extended-release tablets of plasticised solid dispersions of poly(ethylene oxide) (PEO)/polycaprolactone (PCL) and FBZ was investigated due to their unique suitability for semi-continuous manufacturing of pharmaceutical oral solid dosage forms. High-performance liquid chromatography (HPLC) analysis demonstrated a consistent and uniform drug content in the tablets. Thermal analysis using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the amorphous state of the active ingredient, which was endorsed by powder X-ray diffraction spectroscopy (pXRD). Fourier transform infrared spectroscopy (FTIR) analysis did not display any new peak indicative of either a chemical interaction or degradation. Scanning electron microscopy (SEM) images showed smoother surfaces and broader pores as we increased the PCL content. Electron-dispersive X-ray spectroscopy (EDX) revealed that the drug was homogeneously distributed within the polymeric matrices. Drug release studies attested that all moulded tablets of amorphous solid dispersions improved the drug solubility, with the PEO/PCL blend-based matrices showing drug release by Korsmeyer-Peppas kinetics. Thus, HME coupled with µIM proved to be a promising approach towards a continuous automated manufacturing process for the production of oral solid dispersions of benzimidazole anthelmintics to grazing cattle.

Keywords: animal health; extended-release; fenbendazole; hot-melt extrusion; micro-injection moulding; solid dispersion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dimensions of the µIM cavities in the shape of tablet and capsule modelled in Autodesk AutoCAD 2021.
Figure 2
Figure 2
Melt flow index readings from extrudate granules of SDF 1, SDF 2, and SDF 3.
Figure 3
Figure 3
Digital photographs (ShuttlePix Digital Microscope, Nikon Corporation, Tokyo, Japan) displaying the physical aspects of µIM tablets: (a) SDF 1, (b) SDF 2, and (c) SDF 3.
Figure 4
Figure 4
(a) DSC and (b) TGA thermograms of FBZ, PEO powder, PCL powder, SDF 1, SDF 2, and SDF 3.
Figure 5
Figure 5
FTIR spectra of FBZ, PEO powder, PCL powder, SDF 1, SDF 2, and SDF 3.
Figure 6
Figure 6
XRD diffraction patterns of FBZ, PEO powder, PCL powder, SDF 1, SDF 2, and SDF 3.
Figure 7
Figure 7
SDF 1 (a,b), SDF 2 (d,e), and SDF 3 (g,h) images of the external and internal surfaces from moulded tablets, followed by SDF 1 (c), SDF 2 (f), and SDF 3 (i) spectra revealing the dispersion of FBZ identified by the element sulphur throughout the polymeric matrices.
Figure 8
Figure 8
Dissolution profiles of moulded tablets of SDF 1—PEO 95% + FBZ 5% (w/w) evaluated under pH 2 and pH 5.5.
Figure 9
Figure 9
Dissolution profiles of moulded tablets of SDF 2—PEO/FBZ 65% + PCL 35% (w/w), followed by SDF 3—PEO/FBZ 55% + PCL 45% (w/w) evaluated under pH 2 and pH 5.5.
Figure 10
Figure 10
Digital photographs (ShuttlePix Digital Microscope, Nikon Corporation, Tokyo, Japan) of moulded tablets based on PEO and PCL blends after exposure to the dissolution medium at pH 2: (a) SDF 2 and (c) SDF 3, and pH 5.5: (b) SDF 2 and (d) SDF 3.
Figure 11
Figure 11
Percentage of mass loss from moulded tablets based on PEO and PCL blends after 21 days of exposition to dissolution medium at pH 2 and pH 5.5.
See this image and copyright information in PMC

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