TY - JOUR
T1 - Compatibility Study Between Fenbendazole and Poly(Ethylene Oxide) with Application in Solid Dispersion Formulations Using Hot-Melt Extrusion
AU - Bezerra, Gilberto Silva Nunes
AU - Colbert, Declan Mary
AU - O’Donnell, Crevan
AU - Cao, Zhi
AU - Geever, Joseph
AU - Geever, Luke
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/3
Y1 - 2023/3
N2 - Fenbendazole (fen) or methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate is a broad-spectrum anthelmintic from the class of organic compounds known as benzimidazoles. Despite its pharmacological potential, fen has a limited application in oral pharmaceutical dosage forms due to its low aqueous solubility leading to an unsatisfactory bioavailability. This work aims to evaluate the compatibility between fen and poly(ethylene oxide) (PEO) applying differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), followed by the processing of solid dispersions using hot-melt extrusion (HME) with thermal evaluation by DSC, drug dispersion assessment by scanning electron microscopy (SEM) with electron-dispersive X-ray spectroscopy (EDX), and drug release profile by ultraviolet–visible spectroscopy (UV–Vis). The results obtained from the compatibility study using thermal and non-thermal techniques proved that fen and PEO are compatible. The thermal analysis of solid dispersions showed that the extrusion process increases the polymer’s crystalline content when compared to powder mixtures. It also demonstrated that PEO dissolves fen crystalline structure, thus converting it to an amorphous state. SEM with EDX showed that solid dispersions had a homogeneous distribution of fen in the polymeric matrix with the presence of voids, pores, and ducts. Dissolution testing proved that solid dispersions of fen 5% and PEO 95% processed at 50 rpm was able to improve significantly the drug solubility in water-based media. Thus, this work brings a new solution to improving the poor-water solubility of fen using PEO to develop solid dispersion formulations processed by HME.
AB - Fenbendazole (fen) or methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate is a broad-spectrum anthelmintic from the class of organic compounds known as benzimidazoles. Despite its pharmacological potential, fen has a limited application in oral pharmaceutical dosage forms due to its low aqueous solubility leading to an unsatisfactory bioavailability. This work aims to evaluate the compatibility between fen and poly(ethylene oxide) (PEO) applying differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), followed by the processing of solid dispersions using hot-melt extrusion (HME) with thermal evaluation by DSC, drug dispersion assessment by scanning electron microscopy (SEM) with electron-dispersive X-ray spectroscopy (EDX), and drug release profile by ultraviolet–visible spectroscopy (UV–Vis). The results obtained from the compatibility study using thermal and non-thermal techniques proved that fen and PEO are compatible. The thermal analysis of solid dispersions showed that the extrusion process increases the polymer’s crystalline content when compared to powder mixtures. It also demonstrated that PEO dissolves fen crystalline structure, thus converting it to an amorphous state. SEM with EDX showed that solid dispersions had a homogeneous distribution of fen in the polymeric matrix with the presence of voids, pores, and ducts. Dissolution testing proved that solid dispersions of fen 5% and PEO 95% processed at 50 rpm was able to improve significantly the drug solubility in water-based media. Thus, this work brings a new solution to improving the poor-water solubility of fen using PEO to develop solid dispersion formulations processed by HME.
KW - Compatibility study
KW - Fenbendazole
KW - Hot-melt extrusion
KW - Poly(ethylene oxide)
KW - Solid dispersion formulation
UR - http://www.scopus.com/inward/record.url?scp=85127602634&partnerID=8YFLogxK
U2 - 10.1007/s12247-022-09644-y
DO - 10.1007/s12247-022-09644-y
M3 - Article
AN - SCOPUS:85127602634
SN - 1872-5120
VL - 18
SP - 262
EP - 274
JO - Journal of Pharmaceutical Innovation
JF - Journal of Pharmaceutical Innovation
IS - 1
ER -