Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 509, Issue 1-2, Pages 285-295Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2016.05.068
Keywords
Amorphous solid dispersion; Spray drying; Miscibility; Solid-state; Interaction; Thermodynamics
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Funding
- University of Connecticut
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Amorphous solid dispersions typically suffer storage stability issues due to: their amorphous nature, high drug loading, uneven drug: stabilizer ratio and plasticization effects as a result of hygroscopic excipients. An extensive solid state miscibility study was conducted to aid in understanding the mechanisms involved in drug/stabilizer interactions. ABT-102 (model drug) and nine different polymers with different molecular weights and viscosities were selected to investigate drug/polymer miscibility. Three different polymer: drug ratios (1:3, 1:1 and 3:1, w/w) were analyzed using: DSC, FTIR and PXRD. Three different techniques were used to prepare the amorphous solid dispersions: serial dilution, solvent evaporation and spray drying. Spray drying was the best method to obtain amorphous solid dispersions. However, under certain conditions amorphous formulations could be obtained using solvent evaporation. Melting point depression was used to calculate interaction parameters and free energy of mixing for the various drug polymer mixtures. The spray dried solid dispersions yielded a negative free energy of mixing which indicated strong drug-polymer miscibility compared to the solvent evaporation and serial dilution method. Soluplus was the best stabilizer compared to PVP and HPMC, which is probably a consequence of strong hydrogen bonding between the two C=O moieties of soluplus and the drug N-H moieities. (C) 2016 Published by Elsevier B.V.
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