Crystallization of Amorphous Pharmaceuticals at Ambient and Elevated Pressure Conditions
Currently, the pharmaceutical industry is struggling with the problem of solubility-limited bioavailability of marketed and newly synthesized Active Pharmaceutical Ingredients (APIs). The conversion of these APIs into its amorphous form is, without a doub
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Abstract Currently, the pharmaceutical industry is struggling with the problem of solubility-limited bioavailability of marketed and newly synthesized Active Pharmaceutical Ingredients (APIs). The conversion of these APIs into its amorphous form is, without a doubt, a solution for this serious problem. There is, however, one main limiting factor of widespread use of these drugs. Amorphous materials are thermodynamically unstable, and therefore, during the time of storage or manufacturing, they might revert to their crystalline form. In this chapter, we describe the main factors responsible for the re-crystallization of an amorphous APIs. Special attention is paid on differences between the physical stability of amorphous pharmaceuticals stored at standard and manufacturing storage conditions. Keywords Broadband Dielectric Spectroscopy · Crystallization · Physical stability · Elevated pressure · Amorphous pharmaceutical · Solubility limit
Abbreviations APIs AG ASD ARP BIC BCS
Active Pharmaceutical Ingredients Adam and Gibbs model Amorphous Solid Dispersion Aripiprazol Bicalutamide Biopharmaceutics Classification System
J. Knapik-Kowalczuk · K. Chmiel · M. Paluch (B) Faculty of Science and Technology, Institute of Physics, University of Silesia, SMCEBI, 75 Pułku Piechoty 1a, 41-500 Chorzow, Poland e-mail: [email protected] J. Knapik-Kowalczuk e-mail: [email protected] K. Chmiel e-mail: [email protected] © Springer Nature Switzerland AG 2020 T. A. Ezquerra and A. Nogales (eds.), Crystallization as Studied by Broadband Dielectric Spectroscopy, Advances in Dielectrics, https://doi.org/10.1007/978-3-030-56186-4_3
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BDS DSC EZB FLU G-T HN HME KVA LDL NPC1L1 NIM NSAID NMR PCS PVAc PVP PALS PBC QENS R&D SOP TMDSC THz TSDC TTS VFT XRD
J. Knapik-Kowalczuk et al.
Broadband Dielectric Spectroscopy Differential Scanning Calorimetry Ezetimibe Flutamide Gordon-Taylor Havriliak-Negami Hot Melt Extrusion Kollidon VA64® Low-density lipoprotein Niemann-Pick C1-Like1 Nimesulid Non-steroidal anti-inflammatory drug Nuclear Magnetic Resonance Photon Correlation Spectroscopy Poly vinylacetate Poly vinylpyrrolidone Positron Annihilation Lifetime Spectroscopy Probucol Quasielastic Neutron Scattering Research and Development Soluplus® Temperature-Modulated Differential Scanning Calorimetry Terahertz spectroscopy Thermally Stimulated Depolarization Current Time–Temperature Superposition Vogel−Fulcher−Tammann equation X-ray diffraction
1 Introduction The Biopharmaceutics Classification System (BCS) categorizes Active Pharmaceutical Ingredients (APIs) based on their aqueous solubility and intestinal permeability into four groups [1]. Drugs belonging to BCS class I are characterized by high permeability and high solubility. Pharmaceuticals from II BCS class have also high permeability, but unfortunately, they reveal low solubility. The opposite situation, i.e. high solubility but low permeability, can be found in APIs from BCS class III, while the last—IV—BCS group consists of drugs revealing low
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