Formulation and Evaluation of Fenbendazole Extended-Release Extrudes Processed by Hot-Melt Extrusion

Abstract

This study aimed to demonstrate the feasibility of hot-melt extrusion in the development of extended-release formulations of Fenbendazole (Fen) dispersed in PEO/PCL blend-based matrices. Their thermal, physical, chemical and viscosity properties were assessed by differential scanning calorimetry, thermogravimetric analysis/derivative thermogravimetry, Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy, and melt flow index. Drug dispersion was analyzed by scanning electron microscopy with electron dispersive X-ray spectroscopy, and drug release was evaluated by ultraviolet-visible spectroscopy. A thermal analysis indicated the conversion of the drug to its amorphous state. FTIR analysis endorsed the thermal studies pointing to a decrease in the drug's crystallinity with the establishment of intermolecular interactions. XRD analysis confirmed the amorphous nature of Fen. MFI test revealed that PCL acts as a plasticizer when melt-processed with PEO. SEM images displayed irregular surfaces with voids and pores, while EDX spectra demonstrated a homogeneous drug distribution throughout the polymeric carrier. Dissolution testing revealed that PCL retards the drug release proportionally to the content of such polymer incorporated. These melt-extruded matrices showed that the drug release rate in a PEO/PCL blend can easily be tailored by altering the ratio of PCL to address the issues related to the multiple-dosing regimen of Fen in ruminants.

Keywords: extended-release; fenbendazole; hot-melt extrusion.

Figure 1

Chemical structures of (a) Fen, (b) PEO and (c) PCL designed using MarvinSketch 15.4.6.

Figure 2

(a) DSC and (b) TGA curves superposition of Fen (red), formulation 1 (black), formulation 2 (blue), formulation 3 (green), PEO extruded (pink) and PCL extruded (orange) at heating rate of 10 °C min⁻¹.

Figure 3

(a) FTIR spectra and (b) XRD diffraction patterns of Fen (red), formulation 1 (black), formulation 2 (blue), formulation 3 (green), PEO extruded (pink) and PCL extruded (orange).

Figure 4

XRD shows the diffraction peaks of PEO powder (black), PEO extrudate (red), PCL powder (blue) and PCL extrudate (green).

Figure 5

Melt flow index readings for P = powder and E = extrudate of PEO and PCL at 80, 100 and 120 °C.

Figure 6

SEM images of formulation 1 (a,b), formulation 2 (d,e) and formulation 3 (g,h) showing the topography and morphology of extrudates followed by EDX analysis of formulation 1 (c), formulation 2 (f) and formulation 3 (i) showing the homogeneous distribution of the element sulfur from Fen within PEO/PCL blends.

Figure 7

Cumulative release percentage of Fen from formulation 1, formulation 2 and formulation 3 in phosphate buffer media.