Amorphous Stabilization and Dissolution Enhancement of Amorphous Ternary Solid Dispersions: Combination of Polymers Showing Drug–Polymer Interaction for Synergistic Effects

The purpose of this study was to understand the combined effect of two polymers showing drug–polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2014-11, Vol.103 (11), p.3511-3523
Main Authors: Prasad, Dev, Chauhan, Harsh, Atef, Eman
Format: Article
Language:English
Subjects:
Acrylates - chemistry
amorphous
Chemistry, Pharmaceutical
Crystallization Inhibition
Drug Carriers
Drug Stability
Indomethacin
Indomethacin - chemistry
Interaction
Kinetics
Models, Chemical
Polymer
Polymers - chemistry
poorly water-soluble drugs
Povidone - chemistry
solid dispersion
Solubility
Spectrophotometry, Infrared
Spectrum Analysis, Raman
supersaturation
Technology, Pharmaceutical - methods
Transition Temperature
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Summary:The purpose of this study was to understand the combined effect of two polymers showing drug–polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%–40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug–polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3511–3523, 2014
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.24137