Chemistry Reference
In-Depth Information
10.2 MATERIALS SELECTION
All materials used in a hot melt extrusion process have high potential to be intimately
mixed, often forming new molecular interactions between active pharmaceutical ingre-
dient (API)
excipient and eliminating the molecular interactions
that existed in the single-component states of each material. Each component may
signi
-
excipient and excipient
-
finished product, even if present at low
concentration. This feature creates both challenges and opportunities for the formulator
using HME. Irrespective of the drug delivery application of an HME formula or the
excipients used, robust characterization of the API
cantly impact the properties of an HME
-
excipient and possibly excipient
-
excipient interactions in the
final product is important.
10.2.1 Polymers
It is typical to initiate HME formulation development in a stepwise manner, beginning
with drug/polymer binary mixtures before advancing to multicomponent mixtures. Many
polymeric excipients are available for inclusion in hot melt extrusion processes. For solid
dispersions of poorly soluble drugs, a polymer with some hydrophilic properties is
desired along with the capability to form intermolecular interactions with the drug.
Ideally, preformulation data will be available to screen candidate polymers and identify
candidates that exhibit some miscibility with the drug molecule and have the opportunity
to maintain a physically stable dispersed phase.
The most important physical property of polymers used in HME is melt viscosity, so
that the heat-induced (i.e., thermoplastic behavior) and possibly shear-induced (i.e.,
thixotropic behavior) liquid
cient to provide controlled movement of material
through the extruder. Many polymers meet these requirements, either alone or with
plasticizer. Crowley et al. [3] provide extensive overview of polymers used for hot melt
extrusion applications. If seen from the industrial viewpoint for products formulated
using hot melt extrusion or solid dispersions in general, it can be concluded that most
prominent polymers are as follows:
flow is suf
1. Copovidone (Kollidon
VA 64 or Plasdone
S-630)
2. Povidone (Kollidon 12/17 or Plasdone K-12/K-17)
3. HPMC-AS
4. Polyethylene oxide (e.g., Polyox
)
5. Polyethylene glycol
6. HPMC-E5
7. Methacrylates (e.g., EUDRAGIT
E)
Besides these polymers used in industrial applications, a large variety of other
polymers are suitable for hot melt extrusion applications. BASF launched in 2009 under
the brand Soluplus
the
first polymer developed speci
cally for hot melt extrusion
applications. Soluplus is a polyvinyl caprolactam
-
polyvinyl acetate
-
polyethylene glycol
