Abstract
Amorphous solid dispersions (ASDs) offer a means to enhance oral bioavailability of poorly water soluble drugs. However, poor dissolution performance is one of the major challenges encountered in design of ASD based drug products. This study attempts to understand the role of solid-liquid interactions in dissolution behavior of an encapsulated ASD. Capsule dissolution of a molecularly interacting amorphous celecoxib solid dispersion (ACSD), comprising of amorphous celecoxib (A-CLB), polyvinylpyrrolidone (PVP) and meglumine (7:2:1 w/w), displayed non-dispersible plug formation, resulting in fall in the dissolution advantage. The solid dispersion displayed suppressed drug recrystallization during dissolution, studied using XRPD and DSC, and thus it was not the major contributor to this phenomenon. Also, evaluation of physical mixture of ACSD components (PM-ACSD) negated the role of PVP binder properties. Further, FTIR analysis of wet samples revealed that PVP component of ACSD exhibited partial bonding with water (shift of PVP carbonyl stretch from 1658 to 1654 cm-1) as compared to that shown by PM-ACSD (shift from 1658 to 1646 cm-1). This indicated formation of water-PVP-A-CLB hydrogen bond interlinks during ACSD dissolution. Consequently, these interactions graduated to interparticle level. Measurement of crushing strength for dry and hydrated compacts, using texture analysis, showed 7-fold increase in ACSD compact strength as compared to 3-fold for PM-ACSD compact. The findings suggested a significant impact of intermolecular interactions of the solid dispersion on its dosage form drug release, which (i) altered PVP's functionality and (ii) promoted interfacial cohesive interactions via water mediated hydrogen bonds, resulting in solid mass agglomeration. The study emphasis on understanding surface interactions occurring during dissolution, to aid in rationalized design of ASD based drug products.
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