Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 100, Issue 6, Pages 2460-2468Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22462
Keywords
amorphous; solid dispersion; dissolution; solid-state; solid-state transformation during dissolution; celecoxib; solid-liquid interactions; physical characterization
Funding
- Indian Council of Medical Research (New Delhi, India)
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Poor dissolution performance is one of the challenges encountered in dosage form design of amorphous solid dispersions (ASDs). This study was aimed to investigate the effect of solid-liquid interactions of an encapsulated ASD on drug release. Drug release profiles of a molecularly interacting amorphous celecoxib solid dispersion (ACSD) comprising of amorphous celecoxib (A-CLB), polyvinylpyrrolidone (PVP), andmeglumine (7:2: 1, w/w) were compared with crystalline CLB (C-CLB), in powder and capsule form. Although, ACSD powder displayed 28-to 50-fold higher dissolution efficiency at 60 min (DE60), the DE60 in the encapsulated state were drastically reduced due to the formation of a nondispersible plug. The accompanied physical and compositional changes were investigated using X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, and chromatographic techniques. ACSD displayed optimal wettability, sustained A-CLB-PVP interactions, and suppressed phase transformations in aqueous media. Furthermore, Fourier transform infrared and texture analysis revealed role of intermolecular interactions of the solid dispersion, which (i) altered PVP's functionality and (ii) promoted interparticle cohesivity via water-mediated hydrogen bonds, resulting in solid mass agglomeration. Parallel evaluation of A-CLB, physical mixture of ACSD components, and C-CLB solid dispersion supported the above inferences. On the basis of these findings, rationalized formulation approaches for ASD-based drug products are discussed. (C) 2011 WileyLiss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2460-2468, 2011
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