title: The peculiar behavior of the glass transition temperature of amorphous drug-polymer films coated on inert sugar spheres.
abstract: Fluid bed coating has been proposed in the past as an alternative technology for manufacturing of drug-polymer amorphous solid dispersions, or so-called glass solutions. It has the advantage of being a one-step process, and thus omitting separate drying steps, addition of excipients, or manipulation of the dosage form. In search of an adequate sample preparation method for modulated differential scanning calorimetry analysis of beads coated with glass solutions, glass transition broadening and decrease of the glass transition temperature (Tg ) were observed with increasing particle size of crushed coated beads and crushed isolated films of indomethacin (INDO) and polyvinylpyrrolidone (PVP). Substituting INDO with naproxen gave comparable results. When ketoconazole was probed or the solvent in INDO-PVP films was switched to dichloromethane (DCM) or a methanol-DCM mixture, two distinct Tg regions were observed. Small particle sizes had a glass transition in the high Tg region, and large particle sizes had a glass transition in the low Tg region. This particle size-dependent glass transition was ascribed to different residual solvent amounts in the bulk and at the surface of the particles. A correlation was observed between the deviation of the Tg from that calculated from the Gordon-Taylor equation and the amount of residual solvent at the Tg of particles with different sizes.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg O&N2, Leuven 3000, Belgium.
authors.forename: Aswin
authors.initials: A
authors.lastname: Dereymaker
authors.forename: Guy
authors.initials: G
authors.lastname: Van Den Mooter
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D005898:Glass / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D044366:Transition Temperature
chemical_list: D002241:Carbohydrates; D004364:Pharmaceutical Preparations; D011108:Polymers
keywords: amorphous; bead coating; fluid bed coating; glass transition; modulated differential scanning calorimetry; residual solvent; rotary evaporation; solid dispersion; thermal analysis; thermogravimetric analysis