Chemistry Reference
In-Depth Information
graft copolymer. Due to its amphiphilic nature, it is a polymeric emulsi
er that is suitable
for obtaining glassy solid solutions with APIs.
Once lead polymer(s) are selected, consideration must be given to processing
temperatures. It is important to pay particular attention to the product (i.e., dispersion)
melt temperature, and that there can be a signi
s barrel
temperature and the product temperature in the extruder. The following are the other key
process considerations:
cant delta between the extruder
'
1. Selecting process temperatures at which polymer has reduced viscosity but
avoids chemical degradation.
2. Selecting process temperatures at which API can melt and/or solubilize in
polymer, but avoid chemical degradation.
3. Selecting process temperatures at which the drug
-
polymer dispersion can be
extruded to yield a processable solid upon cooling.
The melting temperatures and glass transition temperatures of drug and polymer
support the selection of process temperature. It is common to target process temperatures
20
50 K above polymer
T
g
. Depending on drug loading in the polymer and its solubility
rate in molten polymer, the drug does not need to exceed its melting temperature for
successful solid dispersion formation by HME. If a dispersion forms in the extruder, the
miscible drug may have a large effect on dispersion
T
g
. Predictions of dispersion
T
g
should be made using approaches such as in Ref. [4] to support selection of suitable
process temperatures (see Chapter 9 for description of
T
g
prediction theory and methods).
Often the
T
g
of the amorphous active ingredient is lower than the polymer
T
g
, producing a
plasticizing effect that creates the risk of extrudate lacking the targeted room-temperature
physical properties for simple downstream processing. For example, a lack of brittle
behavior at room temperature may prevent preparation of a granule or pellet-size
extrudate as the material is too soft for milling or cutting operations.
Polymer selection for HME formulation feasibility represents the initial step toward
designing a viable solid dispersion formulation. It provides the basis for a viable HME
process and a carrier excipient that can stabilize drug in the targeted dispersed state.
Additional components will likely be introduced into the extrudate formula to optimize
the manufacturing conditions and the physical and chemical properties of the extruded
material.
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10.2.2 Plasticizers
Plasticizers may be used to aid the HME process by lowering thermal transition
temperatures of individual components and the extruded product. Polymers with high
T
g
values or a complex temperature
viscosity relationship, for example, HPMC poly-
mers, are common candidates for plasticization. To function, the plasticizer must melt at
the target process temperatures and be miscible with at least one component of the
formulation. Common plasticizers include low and medium molecular weight poly-
ethylene glycols, poloxamers, and triethyl citrate.
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