Chemistry Reference
In-Depth Information
TABLE 2 . 6 . Typical Bond Energy and Relative Strength of Intermolecular Forces
Type of Interaction
Bond Energy (kJ/mol)
Approximate Relative Strength
Ionic interactions
850-1700
1000
Hydrogen bonding
50-170
100
Dipole-dipole interaction
2-8
10
van der Waals interaction
∼
1
1
Adapted with permission from Ref. 79.
More recent approaches have utilized interactions measured by DSC in combination with
Flory
-
Huggins solution theory to construct drug
-
polymer phase diagrams [82].
The performance and stability of ASDs are drastically
impacted by moisture that is always present even in systems that are considered dry. As
such, the hygroscopicity of the polymer is a key parameter in the long-term chemical and
physical stability of any ASD. The chemical stability can be impacted through increased
hydrolytic degradation caused by the increased presence of water [83]. In addition, water
can act as a plasticizer in an ASD causing the overall
T
g
to lower and thus increase
molecular mobility [84]. Another mechanism by which water can destabilize amorphous
dispersions is by disrupting the interactions between a drug and a polymer resulting in
phase separation and eventual crystallization of the drug [85]. The myriad of problems
caused by the absorption of water into an ASD have resulted in the suggestion that
polymers with low or no water solubility such as methacrylates and HPMCAS will help
stabilize ASDs by minimizing water interactions [74].
2.4.1.4 Hygroscopicity
2.4.2 Preparation of Amorphous Solid Dispersions
In addition to determining how well a drug is stabilized in the amorphous dispersion, the
physical properties of the polymers, surfactants, and drug also in
uence the method
utilized to create the solid dispersion. While spray drying and HME are the most
industry-relevant techniques to produce ASDs, there are many techniques that can be
utilized. Such techniques, which include supercritical
fluid processing, co-grinding, melt
quenching, and
fluid bed layering, are limited in use for reasons such as poor or partial
conversion and slow rates of conversion.
Spray drying is a robust industrial process utilized to transform a solution, slurry,
suspension, or emulsion into a dry powder. For pharmaceutical applications, the process
has been reviewed in the literature [86] and is covered in detail in Chapter 9. The spray
drying procedure entails the atomization of the feed solution that contains the drug and
the carrier agent through a nozzle. The atomized droplets are mixed with heated drying
gas that rapidly evaporates the solvent from the droplets. The resulting particles are then
isolated via a
filter or cyclone and further dried as necessary. Through the control of
process parameters such as feed solution
flow rate and pressure, drying gas inlet and
outlet temperatures, and
flow rates, the size, shape, and bulk density of the resulting
particles can be tailored. Among the advantages of spray drying are the rapid removal of
