title: Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.
abstract: 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.
authors.affiliation: School of Pharmacy, MCPHS University-Boston, Boston, Massachusetts 02115.
authors.forename: Dev
authors.initials: D
authors.lastname: Prasad
authors.affiliation: School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska 68178.
authors.forename: Harsh
authors.initials: H
authors.lastname: Chauhan
authors.affiliation: School of Pharmacy, MCPHS University-Boston, Boston, Massachusetts 02115. Electronic address: eman.atef@mcphs.edu.
authors.forename: Eman
authors.initials: E
authors.lastname: Atef
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature
chemical_list: D000179:Acrylates; D004337:Drug Carriers; C477020:Eudragit E100; D011108:Polymers; D011205:Povidone; D007213:Indomethacin
keywords: Crystallization Inhibition; Indomethacin; Interaction; Polymer; amorphous; poorly water-soluble drugs; solid dispersion; solubility; supersaturation