Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution

de Assis, João M.C.; Barbosa, Eduardo J.; Bezzon, Vinícius D.N.; Lourenço, Felipe R.; Carvalho, Flavio M.S.; Matos, J. R.; Araci Bou-Chacra, Nadia; Benmore, Chris J.; Byrn, Stephen R.; Costa, Fanny N.; de Araujo, Gabriel L.B.

doi:10.1016/j.ijpharm.2022.121456

Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution

Journal Article · Mon Jan 10 00:00:00 EST 2022 · International Journal of Pharmaceutics

DOI:https://doi.org/10.1016/j.ijpharm.2022.121456· OSTI ID:1878355

de Assis, João M.C. ^[1]; Barbosa, Eduardo J. ^[1]; Bezzon, Vinícius D.N. ^[2]; Lourenço, Felipe R. ^[1]; Carvalho, Flavio M.S. ^[1]; Matos, J. R. ^[1]; Araci Bou-Chacra, Nadia ^[1]; Benmore, Chris J. ^[3]; Byrn, Stephen R. ^[4]; Costa, Fanny N. ^[5]; de Araujo, Gabriel L.B. ^[1]

Univ. of Sao Paulo (Brazil)
Federal Univ. of ABC, Santo Andre, SP (Brazil)
Argonne National Lab. (ANL), Argonne, IL (United States)
Purdue Univ., West Lafayette, IN (United States)
Harwell Science and Innovation Campus, Didcot (United Kingdom)

The FDA-approved anthelmintic flubendazole has shown potential to be repositioned to treat cancer and dry macular degeneration; however, its poor water solubility limits its use. Amorphous solid dispersions may overcome this challenge, but the balance of excipients may impact the preparation method and drug release. Here, we evaluate the influence of adjuvants and drug loading on the development of an amorphous solid dispersion of flubendazole-copovidone by hot-melt extrusion. The drug, copovidone, and adjuvants (magnesium stearate and hydroxypropyl cellulose) mixtures were statistically designed, and the process was performed in a twin-screw extruder. The study showed that flubendazole and copovidone mixtures were highly extrudable, except when drug loading was high (>40%). Furthermore, magnesium stearate positively impacted the extrusion and was more effective than hydroxypropyl cellulose. The extruded materials were evaluated by modulated differential scanning calorimetry and X-ray powder diffraction, obtaining positive amorphization and physical stability results. Pair distribution function analysis indicated the presence of drug rich domains with medium-range order structure and no evidence of polymer-drug interaction. All extrudates presented faster dissolution (HCl, pH 1.2) than pure flubendazole, and both adjuvants had a notable influence on the dissolution rate. In conclusion, hot-melt extrusion may be a viable option to obtain stable flubendazole: copovidone amorphous dispersions.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: Brazilian Ministry of Higher Education, Coordination for the Improvement of Higher Education Personnel (CAPES) Program; Sao Paulo Research Foundation (FAPESP); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1878355

Journal Information:: International Journal of Pharmaceutics, Journal Name: International Journal of Pharmaceutics Vol. 614; ISSN 0378-5173

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
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Hot-melt extrusion
Hydroxypropyl cellulose
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Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution

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