Compatibility Study Between Fenbendazole and Poly(Ethylene Oxide) with Application in Solid Dispersion Formulations Using Hot-Melt Extrusion

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

“…Fen is a crystalline powder represented by two endothermic peaks, one at 244 °C (Δ H m = 252 J g −1 ) characteristic of the sample melting transition, followed by a second peak at 271 °C (Δ H m = 27 J g −1 ) representing its decomposition. Other studies have reported the same thermal profile for Fen, exhibiting the melting event followed by decomposition [ 14 , 15 , 20 ].…”

“…It converts the API’s crystalline structure into its amorphous state and blends both API and polymer chains at the molecular level, due to the high sheer force of the process usually requiring a temperature above the API’s melting point ( T m ) [ 21 ]. However, studies have proved the possibility of processing solid dispersion formulations below the original melting point of the drug [ 14 , 22 ] since the interactions between drug and polymers may depress the API’s chemical potential, which causes the fusion to take place below the usual T m [ 21 ].…”

“…Fen melting peak could not be visualized in the formulations’ thermograms, which can be explained by the capacity of PEO/PCL blends to melt first during melt-processing solubilizing Fen’s crystalline structure, converting it into its amorphous state and creating intermolecular interactions between the drug and polymers [ 14 ]. In another study with PEO and etofylline, only the polymer melting peak was evident in the thermogram, so the absence of the API’s phase transition indicates its complete dissolution in the polymer’s amorphous regions [ 23 ].…”

“…PEO 95% and Fen 5% ( w / w ) were weighed and mixed manually before melt processing. Extrudates were air-cooled and granulated using Colortronic rough granulator machine [ 14 ].…”

“…PEO is a semi-crystalline, hydrophilic, thermoplastic polymer capable of hydrating and swelling in contact with water, which makes PEO vastly applied in controlled-release tablets [ 13 ]. Since PEO processed by HME has proven to increase Fen dissolution properties demonstrating fast drug release rates [ 14 ], we hypothesized that blending PEO with a biodegradable aliphatic polyester as PCL, which is a highly hydrophobic and crystalline polymer able to degrade very slowly, would retard Fen release rates.…”