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

[Display omitted] 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)...

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Bibliographic Details
Published in:International journal of pharmaceutics 2021-05, Vol.600, p.120500, Article 120500
Main Authors: Bezzon, Vinicius D.N., Ferreira, Fabio F., Smith, Pamela, Benmore, Chris J., Byrn, Stephen R., de Araujo, Gabriel L.B.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Amorphous structure
Flubendazole
Hypromellose derivatives
Pair distribution function
Polymeric matrices
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Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2021.120500