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

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.

Functionalized polypropylene separator coated with polyether/polyester blend for high-performance lithium metal batteries

“…As shown in Figure 3A, the decomposition temperature of PP separators is around 400 °C. Although the decomposition temperature of coated separators is slightly decreased to 377 °C because of the lower decomposition temperature of polymer coatings [39,40] , they are still enough for battery application. As shown in Figure 3B, the PP-PEO 60w (EO:Li + = 8:1) and PP-blended PEO 60w /PCL 5w separators show improved thermal stability compared to the commercial PP separator.…”

Development of a multi-component gastroretentive expandable drug delivery system (GREDDS) for personalized administration of metformin

“…Indeed, it was proposed for the fabrication of controlled-release DDSs to be orally administered, even resorting to novel manufacturing approaches (e.g. injection molding, 3D printing, electrospinning) [24,25,27,[92][93][94][95].…”

Preparation and evaluation of fenbendazole methyl-β-cyclodextrin inclusion complexes

“…Fenbendazole loaded with Mobil composition of matter number 41 showed enhanced delivery capability to PC-3 cells [14], the micelles containing fenbendazole and rapamycin (1:2 ratio) prepared via freeze-drying showed slower release in vitro [15], fenbendazole-encapsulated poly-(D,L-lactide-co-glycolide) acid nanoparticles prepared by an oil-in-water emulsion method [16] could increase water solubility, enhance absorption, and exert significant anti-cancer effects in EOC cells and xenograft models including PDX [17], fenbendazole dispersed in PEO/PCL blendbased matrices prepared by hot-melt extrusion revealed that PCL retarded the drug release proportionally to the content of such polymer incorporated [18]. Compatibility between fenbendazole and three polymeric excipients was evaluated [19], and tablets of plasticized solid dispersions of poly-(ethylene oxide)/polycaprolactone and fenbendazole improved the drug solubility and release [20]. These research works did not make significant solubility improvement and could not reach the requirements for a cancer therapeutic dose (5-10 mg/mL), therefore, more effects need to be put to find new formulation with significant water solubility increasing [21][22][23][24].…”