Chapter 6
Managing Thermal History
to Stabilize/Destabilize Pharmaceutical
Glasses
Kohsaku Kawakami
Abstract Vitrification is a powerful methodology for improving the dissolution of
poorly soluble drugs. Thus, amorphous dosage forms are sometimes employed in the
pharmaceutical industry for enhancing their oral absorption, for which the dissolution
process plays an important role. Amorphous structures change with time because
of their non-equilibrium property, and this impacts their physical stability. Thus,
assurance of their physical stability can be challenging during their development.
Amorphous properties are significantly influenced by their thermal history. Here,
the influence of thermal history on the crystallization behavior of pharmaceutical
glasses is discussed with emphasis on possible nucleation, relaxation, decrease in
free volume, etc., during the thermal treatment. Factors that enhance crystallization
such as mechanical stress and moisture sorption are also discussed.
Keywords Pharmaceutical glass · Crystallization · Nucleation · Thermal history ·
Relaxation
6.1 Introduction
In the pharmaceutical industry, poorly soluble candidates frequently survive
screening studies, hence there is a need to increase their solubility. Amorphous solids,
because of their high energy state, may be employed for this purpose [1–4]. Amorphous drugs are usually stabilized in the form of solid dispersion, and polymeric
excipients are added for improving solid-state stability and dissolution.
Crystallization tendency is compound dependent [5]. Many research groups have
assessed crystallization tendency by applying a cooling/reheating cycle to the melt
using differential scanning calorimetry (DSC). The classification criteria proposed
by Taylor et al. are as follows [6]:
K. Kawakami (B)
International Center for Materials Nanoarchitectonics, National Institute for Materials Science,
1-1 Namiki, Tsukuba 305-0044, Ibaraki, Japan
e-mail: kawakami.kohsaku@nims.go.jp
© Springer Nature Singapore Pte Ltd. 2020
M. Sakamoto and H. Uekusa (eds.), Advances in Organic Crystal Chemistry,
https://doi.org/10.1007/978-981-15-5085-0_6
95
Managing Thermal History
to Stabilize/Destabilize Pharmaceutical
Glasses
Kohsaku Kawakami
Abstract Vitrification is a powerful methodology for improving the dissolution of
poorly soluble drugs. Thus, amorphous dosage forms are sometimes employed in the
pharmaceutical industry for enhancing their oral absorption, for which the dissolution
process plays an important role. Amorphous structures change with time because
of their non-equilibrium property, and this impacts their physical stability. Thus,
assurance of their physical stability can be challenging during their development.
Amorphous properties are significantly influenced by their thermal history. Here,
the influence of thermal history on the crystallization behavior of pharmaceutical
glasses is discussed with emphasis on possible nucleation, relaxation, decrease in
free volume, etc., during the thermal treatment. Factors that enhance crystallization
such as mechanical stress and moisture sorption are also discussed.
Keywords Pharmaceutical glass · Crystallization · Nucleation · Thermal history ·
Relaxation
6.1 Introduction
In the pharmaceutical industry, poorly soluble candidates frequently survive
screening studies, hence there is a need to increase their solubility. Amorphous solids,
because of their high energy state, may be employed for this purpose [1–4]. Amorphous drugs are usually stabilized in the form of solid dispersion, and polymeric
excipients are added for improving solid-state stability and dissolution.
Crystallization tendency is compound dependent [5]. Many research groups have
assessed crystallization tendency by applying a cooling/reheating cycle to the melt
using differential scanning calorimetry (DSC). The classification criteria proposed
by Taylor et al. are as follows [6]:
K. Kawakami (B)
International Center for Materials Nanoarchitectonics, National Institute for Materials Science,
1-1 Namiki, Tsukuba 305-0044, Ibaraki, Japan
e-mail: kawakami.kohsaku@nims.go.jp
© Springer Nature Singapore Pte Ltd. 2020
M. Sakamoto and H. Uekusa (eds.), Advances in Organic Crystal Chemistry,
https://doi.org/10.1007/978-981-15-5085-0_6
95