Amorphous dispersions of flubendazole in hydroxypropyl methylcellulose: Formulation stability assisted by pair distribution function analysis

Bezzon, Vinicius D. N.; Ferreira, Fabio F.; Smith, Pamela; Benmore, Chris J.; Byrn, Stephen R.; de Araujo, Gabriel L. B.

doi:10.1016/j.ijpharm.2021.120500

Amorphous dispersions of flubendazole in hydroxypropyl methylcellulose: Formulation stability assisted by pair distribution function analysis

Journal Article · Sat May 01 04:00:00 EDT 2021 · International Journal of Pharmaceutics

DOI:https://doi.org/10.1016/j.ijpharm.2021.120500· OSTI ID:1781671

Bezzon, Vinicius D. N. ^[1]; Ferreira, Fabio F. ^[2]; Smith, Pamela ^[3]; Benmore, Chris J. ^[4]; Byrn, Stephen R. ^[5]; de Araujo, Gabriel L. B. ^[6]

Federal University of ABC (UFABC), Santo Andre, SP (Brazil); Improved Pharma, West Lafayette, IN (United States)
Federal University of ABC (UFABC), Santo Andre, SP (Brazil)
Improved Pharma, West Lafayette, IN (United States)
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Improved Pharma, West Lafayette, IN (United States); Purdue Univ., West Lafayette, IN (United States)
Univ. of Sao Paulo (Brazil)

Here, we use X-ray pair distribution function (PDF) analysis applied to high-energy synchrotron X-ray powder diffraction data to evaluate the amorphous solid dispersions interactions and their aging stability. The obtained systems are based on hydroxypropyl methylcellulose (hypromellose) derivatives and flubendazole (FBZ) drug dispersions prepared using a spray-dryer technique. We carry out stability studies under aging parameters (40 °C/75% relative humidity) to tune the systems’ recrystallization. The results reveal that ion-base interactions between the drug-polymer matrix are responsible for reducing clustering processes yielding slower recrystallization and different ordering in the hypromellose phthalate (HPMCP/FBZ) and hypromellose acetate succinate (HPMC-AS/FBZ) systems and complete drug clustering in hypromellose (HPMC-E3/FBZ). The structural ordering was accessed using differential X-ray PDFs that revealed the region between 3.5 Å and 5.0 Å could be related to FBZ intermolecular interactions and is more ordered for the least stable system (HPMC-E3/FBZ) and less ordered for the most stable system (HPMCP/FBZ). These results show that the ion-base interactions between drug and matrix occur at these intermolecular distances.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Sao Paulo Research Foundation (FAPESP); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1781671

Journal Information:: International Journal of Pharmaceutics, Journal Name: International Journal of Pharmaceutics Vol. 600; ISSN 0378-5173

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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