title: Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems.
abstract: The correlations between amorphous miscibility/physical stability of binary solid dispersions (a highly crystalline additive-an amorphous polymer) and the physicochemical properties of the components were investigated. Crystalline functional excipients including surfactants, organic acids, and organic bases were prepared in binary solid dispersions in amorphous polymers by solvent evaporation method. Amorphous miscibility and physical stability of the systems were characterized using polarized light microscope, differential scanning calorimeter, and powder X-ray diffraction. Physicochemical parameters (solubility parameter (delta), hydrogen bond energy, Log P, pK(a) value as an indicator of acid-base ionic interaction, and T(g) of the dispersion as a surrogate of system's mobility) were selected as thermodynamic and kinetic factors to examine their influences on the systems' amorphous miscibility and physical stability. All systems possessing acid-base ionic interaction formed amorphous state. In the absence of the ionic interaction, solubility parameter and partition coefficient were shown to have major roles on amorphous formation. Upon storage condition at 25 degrees C/60% RH for 50 days, systems having ionic interaction and high T(g) remained in the amorphous state. This binary system study provides an insight and a basis for formation of the amorphous state of multi-component solid dispersions utilizing their physicochemical properties.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877, USA. seung-uk.yoo@boehringer-ingelheim.com
authors.forename: Seung-uk
authors.initials: SU
authors.lastname: Yoo
authors.forename: Steven L
authors.initials: SL
authors.lastname: Krill
authors.forename: Zeren
authors.initials: Z
authors.lastname: Wang
authors.forename: Chitra
authors.initials: C
authors.lastname: Telang
mesh_terms: D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D008859:Microscopy, Polarization; D012995:Solubility
chemical_list: D005079:Excipients