Crystallization of Amorphous
Pharmaceuticals at Ambient
and Elevated Pressure Conditions
Justyna Knapik-Kowalczuk, Krzysztof Chmiel, and Marian Paluch
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
Active Pharmaceutical Ingredients
AG
Adam and Gibbs model
ASD
Amorphous Solid Dispersion
ARP
Aripiprazol
BIC
Bicalutamide
BCS
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: marian.paluch@us.edu.pl
J. Knapik-Kowalczuk
e-mail: justyna.knapik-kowalczuk@us.edu.pl
K. Chmiel
e-mail: krzysztof.chmiel@smcebi.edu.pl
© 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
55
Pharmaceuticals at Ambient
and Elevated Pressure Conditions
Justyna Knapik-Kowalczuk, Krzysztof Chmiel, and Marian Paluch
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
Active Pharmaceutical Ingredients
AG
Adam and Gibbs model
ASD
Amorphous Solid Dispersion
ARP
Aripiprazol
BIC
Bicalutamide
BCS
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: marian.paluch@us.edu.pl
J. Knapik-Kowalczuk
e-mail: justyna.knapik-kowalczuk@us.edu.pl
K. Chmiel
e-mail: krzysztof.chmiel@smcebi.edu.pl
© 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
55