Chemistry Reference
In-Depth Information
Figure 5.1.
Schematic showing some of the factors important for the optimal performance of
amorphous solid dispersions.
5.2 THEORY OF CRYSTALLIZATION IN THE SOLID STATE
The pure material in the amorphous state has a higher energy than the corresponding
crystalline material, and thus will always have the potential to crystallize [1]. In order to
understand the factors that impact the kinetics of crystallization from amorphous formula-
tions, it is useful to brie
y consider some theoretical concepts pertaining to melt crystalli-
zation. The crystallization process involves two events: nucleation to form an embryonic
crystal followed by growth of that crystal; each of these processes will be brie
y discussed.
5.2.1 Nucleation Theory
Crystallization begins when a small but critical number of molecules of the stable phase
self-assemble to form a nucleus. Nucleation events can be classi
ed as primary and
secondary processes [2]. Primary nucleation occurs in a system that does not contain any
crystalline matter, while secondary nucleation refers to the formation of nuclei in the
vicinity of crystals already present in the system and is more relevant for solution
crystallization where it is often seen. Primary nucleation may occur spontaneously
(homogeneous) or can be induced by the presence of foreign surfaces (heterogeneous).
For most pharmaceutical materials, it is likely that heterogeneous nucleation predominates.
The nucleation rate per unit volume,
J
, from a melt can be described by Equation 5.1:
J
A
exp
Δ
G
*
Δ
G
a
:
(5.1)
k
B
T
