The Peculiar Behavior of the Glass Transition Temperature of Amorphous Drug-Polymer Films Coated on Inert Sugar Spheres

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 (T-g) 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 T-g regions were observed. Small particle sizes had a glass transition in the high T-g region, and large particle sizes had a glass transition in the low T-g 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 T-g from that calculated from the Gordon-Taylor equation and the amount of residual solvent at the T-g of particles with different sizes. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1759-1766, 2015