Chemistry Reference
In-Depth Information
TABLE 6.4.
Important Polymer Properties
Polymer Property
Key Considerations Around Each Parameter
Size/molecular weight
A descriptor of the average size of the polymer. Other parameters,
such as glass transition temperature, are affected by molecular
weight
Polydispersity
A parameter for describing the polymer size distribution
Functional groups present
A consideration for molecular interactions such as hydrogen
bonding, which can affect physical stability, dissolution rate, and
supersaturation properties
Impurity profile
A parameter affecting drug substance chemical stability and
dispersion safety profile
Hydrophilic/lipophilic
balance
A parameter for matching polarity with the drug substance.
Matching polarity may be necessary for favorable
physicochemical interactions affecting physical stability,
dissolution rate, and supersaturation
Ionization state/apparent
p
K
a
A parameter for pH-dependent applications and is predictive of
potential acid/base interactions with the drug substance. Given
the pH gradient that occurs in the digestive tract, ionization state
can be critical to consider for
in vivo
performance
Glass transition
temperature
This thermal parameter is closely linked to the molecular mobility
of an amorphous material
Aqueous solubility and
dissolution rate
Parameters affecting aqueous dissolution, solubilization, and
supersaturation performance
in vitro
and
in vivo
Organic solvent solubility
A parameter to consider for processing via the spray-drying
process
Thermal stability
A parameter to consider for processing via the hot melt extrusion
process
Hygroscopicity
A parameter affecting storage conditions of dispersions and
potential for moisture uptake
Parameters affecting the safety/tolerability pro
le of the polymer
and ability for polymer to be metabolized
in vivo
Biocompatibility
6.3.1 The Impact of Polymer Properties on Dissolution, Solubility,
and Supersaturation
Dissolution of a solid dispersion depends on the proportional quantities and properties of
both the drug and the carrier [71]. Craig presented a simpli
ed model of the process by
which drug particles are released during dissolution [72]. This model assumes that there
is a highly concentrated polymer layer at the dissolving surface (at least at high polymer
content) through which the drug must pass before it is released into the bulk solution
phase. The two main mechanisms for drug release from solid dispersions that have been
described in the literature are carrier drug release and carrier-controlled release [72
75].
For the carrier drug release, the drug is molecularly dispersed within the concentrated
polymer layer and the rate-limiting step for dissolution of drug is the release of polymer
itself. For the carrier-controlled release, the dissolution of the drug particles into the
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