6 Managing Thermal History to Stabilize/Destabilize …
109
6.8 Summary
Crystallization experiments frequently face reproducibility problems. Sometimes it is
unavoidable because of the stochastic property of nucleation, but other cases may be
explained by the difference in thermal history of the materials. In this chapter, influence of thermal history on physical stability (crystallization) was discussed with many
examples. When the glass is prepared by the quench cooling, the target (minimum)
temperature of the cooling process is usually not provided in the literature. However,
it may have a great impact on the crystallization behavior. Ideally, optimal nucleation
and crystal growth temperatures should be comprehended to control the crystallization behavior of the glass. The crystallization tendency of the compounds, though it
is not discussed in this chapter, must also be comprehended well. The cooling rate
also has significant importance in determining the glass property. The relevance of
chemical structure to the sensitivity of the glass property on thermal history requires
more understanding. In addition to thermal history, the importance of other factors
such as surface area, mechanical stress, and sorption of trace amount of moisture
needs to be recognized.
Although there is no doubt that the amorphous state is quite useful in the pharmaceutical field, its practical use is relatively limited, partially because of difficulty
in its handling. Storage of ASDs under freezing temperature sounds appropriate for
the long-term, but it is not true in some cases as observed for celecoxib glass in
this chapter. Since the current crystallization theory was developed with inorganic
compounds in mind, its application to crystallization of small organics requires attention, where the structure is maintained by various strong and weak interactions such
as covalent and noncovalent binding forces. Further understanding of this field should
enable more frequent use of the amorphous state for practical products.
References
1. Kawakami, K.: Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly
absorbed drugs. Adv. Drug Deliv. Rev. 64, 480–495 (2012)
2. Paudel, A., Worku, Z.A., Meeus, J., Guns, S., Van den Mooter, G.: Manufacturing of solid
dispersions of poorly soluble drugs by spray drying: formulation and process considerations.
Int. J. Pharm. 453, 253–284 (2013)
3. Kawakami, K.: Theory and practice of supersaturatable formulations for poorly soluble drugs.
Ther. Deliv. 6, 339–352 (2015)
4. Singh, A.: Spray drying formulation of amorphous solid dispersions. Adv. Drug Deliv. Rev.
100, 27–50 (2016)
5. Kawakami, K.: Crystallization tendency of pharmaceutical glasses: relevance to compound
properties, impact of formulation process, and implications for design of amorphous solid
dispersions. Pharmaceutics 11, 202 (2019)
6. Baird, J.A., van Eerdenbrugh, B., Taylor, L.S.: A classification system to assess the crystallization tendency of organic molecules from undercooled melts. J. Pharm. Sci. 99, 3787–3806
(2010)
109
6.8 Summary
Crystallization experiments frequently face reproducibility problems. Sometimes it is
unavoidable because of the stochastic property of nucleation, but other cases may be
explained by the difference in thermal history of the materials. In this chapter, influence of thermal history on physical stability (crystallization) was discussed with many
examples. When the glass is prepared by the quench cooling, the target (minimum)
temperature of the cooling process is usually not provided in the literature. However,
it may have a great impact on the crystallization behavior. Ideally, optimal nucleation
and crystal growth temperatures should be comprehended to control the crystallization behavior of the glass. The crystallization tendency of the compounds, though it
is not discussed in this chapter, must also be comprehended well. The cooling rate
also has significant importance in determining the glass property. The relevance of
chemical structure to the sensitivity of the glass property on thermal history requires
more understanding. In addition to thermal history, the importance of other factors
such as surface area, mechanical stress, and sorption of trace amount of moisture
needs to be recognized.
Although there is no doubt that the amorphous state is quite useful in the pharmaceutical field, its practical use is relatively limited, partially because of difficulty
in its handling. Storage of ASDs under freezing temperature sounds appropriate for
the long-term, but it is not true in some cases as observed for celecoxib glass in
this chapter. Since the current crystallization theory was developed with inorganic
compounds in mind, its application to crystallization of small organics requires attention, where the structure is maintained by various strong and weak interactions such
as covalent and noncovalent binding forces. Further understanding of this field should
enable more frequent use of the amorphous state for practical products.
References
1. Kawakami, K.: Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly
absorbed drugs. Adv. Drug Deliv. Rev. 64, 480–495 (2012)
2. Paudel, A., Worku, Z.A., Meeus, J., Guns, S., Van den Mooter, G.: Manufacturing of solid
dispersions of poorly soluble drugs by spray drying: formulation and process considerations.
Int. J. Pharm. 453, 253–284 (2013)
3. Kawakami, K.: Theory and practice of supersaturatable formulations for poorly soluble drugs.
Ther. Deliv. 6, 339–352 (2015)
4. Singh, A.: Spray drying formulation of amorphous solid dispersions. Adv. Drug Deliv. Rev.
100, 27–50 (2016)
5. Kawakami, K.: Crystallization tendency of pharmaceutical glasses: relevance to compound
properties, impact of formulation process, and implications for design of amorphous solid
dispersions. Pharmaceutics 11, 202 (2019)
6. Baird, J.A., van Eerdenbrugh, B., Taylor, L.S.: A classification system to assess the crystallization tendency of organic molecules from undercooled melts. J. Pharm. Sci. 99, 3787–3806
(2010)