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

Author(s)

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

Affiliation

^[1] Fed Univ ABC UFABC, Ctr Nat & Human Sci CCNH, BR-09210580 Santo Andre, SP - Brazil

^[2] Improved Pharma, W Lafayette, IN 47906 - USA

^[3] Xray Sci Div, Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 - USA

^[4] Purdue Univ, Dept Ind & Phys Pharm, W Lafayette, IN 47906 - USA

^[5] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, BR-05508900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 600, MAY 1 2021.
• Web of Science Citations: 0

Abstract

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 degrees 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 angstrom and 5.0 angstrom 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. (AU)

• FAPESP's process: 19/04998-2 - Nanocrystalline and amorphous solid dispersions formulations for improvement of antitumor therapies
• Grantee: Gabriel Lima Barros de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/11990-5 - Local structure characterization and stability of amorphous systems
• Grantee: Vinícius Danilo Nonato Bezzon
• Support Opportunities: Scholarships in Brazil - Post-Doctoral