title: Frozen in Time: Kinetically Stabilized Amorphous Solid Dispersions of Nifedipine Stable after a Quarter Century of Storage.
abstract: Kinetically stabilized amorphous solid dispersions are inherently metastable systems. Therefore, such systems are generally considered prone to recrystallization. In some cases, the formation of crystals will impact the bioavailability of the active pharmaceutical ingredient in these formulations. Recrystallization therefore may present a significant risk for patients as it potentially lowers the effective dose of the pharmaceutical formulation. This study indicates that such metastable formulations may indeed remain fully amorphous even after more than two decades of storage under ambient conditions. Different formulations of nifedipine stored for 25 years were compared with freshly prepared samples. A thorough physicochemical characterization including polarized light microscopy, differential scanning calorimetry, X-ray powder diffraction, and transmission Raman spectroscopy was undertaken. This in-depth characterization indicates no signs of recrystallization in the stored samples. The observations presented here prove that long-term stability of amorphous solid dispersions much beyond the typical shelf life for pharmaceutical formulations is indeed possible by kinetic stabilization alone. These findings implicate a reevaluation of the propensity to recrystallize for kinetically stabilized amorphous solid dispersions.
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Frank
authors.identifier: 0000-0002-9396-3118
authors.initials: F
authors.lastname: Theil
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Sankaran
authors.initials: S
authors.lastname: Anantharaman
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Kyeremateng
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: van Lishaut
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Dreis-Kühne
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Mägerlein
authors.affiliation: AbbVie Deutschland GmbH & Co. KG , 67061 Ludwigshafen, Germany.
authors.forename: Gerd H
authors.initials: GH
authors.lastname: Woehrle
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D007700:Kinetics; D009543:Nifedipine / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D009543:Nifedipine
keywords: amorphous solid dispersion; crystallinity; long-term stability; nifedipine; physicochemical characterization; recrystallization