Hot-Melt Extrusion Principle
Hot-Melt Extrusion (HME) technique also called Hot-Melt
Palletization
(HMP) technique, where thermal melting
of material conveyed through a channel, using at least one thermoplastic
polymer or low-melting wax.
It is used in a variety of industries,
most notably in the plastics industry. A key difference of pharmaceutical
extruders is that they must comply with pharmaceutical regulations, including
cleaning and validation. Screw extruders, most notably twin-screw units, are
most commonly used in pharmaceutical applications and hence are the focus here.
Screws can typically be divided into three sections, as follows:
(i) Feeding section
The purpose is to transfer material from
the hopper to the barrel. The channel depth is usually at its largest in this
section, to facilitate mass flow.
(ii) Melting or compression section
The channel depth decreases in this
section, hence increasing the pressure and removing entrapped air. The polymer
also typically begins to soften and melt in this section.
(iii) Metering section
The primary function is to reduce the
pulsating flow and ensure uniform delivery through the die. The extrudate flow
rate is thereby highly dependent on channel depth and section length.
The die at the barrel exit dictates
extrudate shape, whose size generally increases upon exit, a phenomenon known
as “die swell” (the extent of which is mainly governed by the viscoelastic
properties of the polymers). Auxiliary downstream equipment is usually for
product cooling, cutting or collecting.
The screws in twin-screw extruders can
rotate in the same direction (co-rotating) or opposite directions
(counter-rotating), imposing different conditions. The counter-rotating designs
are most common and are utilized when high shear is needed, since the material
is squeezed through the gap between the approaching screws. Counter-rotating
extruders, however, generally suffer from air entrapment, high-pressure
generation, low maximum screw speed and low output.
Materials for HME processing are
selected based on their physicochemical properties and interaction potential.
These can be quantified theoretically, using solubility parameters, or
experimentally, using differential scanning calorimetry or hot-stage
microscopy, with differentials in solubility parameters indicating the
likelihood of material miscibility.
Thermal stability of compounds is a
prerequisite for HME, but thermolabile compounds are not automatically
precluded, due to the relatively short extrusion times. When preparing
amorphous solid dispersions, the mixture is commonly heated above both the
polymer glass transition temperature (Tg), to induce plasticity, and the API
melting point, to facilitate dispersion and conversion to the amorphous state.
API solubility in the carrier generally increases with temperature, resulting
in crystalline APIs either melting or become solubilized in the carrier matrix.
For IR applications, HME is typically used
to prepare milled extrudate for compression or capsule filling (after blending
with excipients), while near-spherical pellets are generally required for CR
applications. For this purpose, tailored shaping devices at the extruder exit
have been developed, typically referred to as die face pelletisers. These cut
the molten material emerging from the die plate into small particles, using a
rotating knife. The spherical shape of these pellets is thereby a result of cutting
the extrudate at a temperature above its softening point, where viscous forces
allow particles to contract and become spherical.
It is important to note that
transforming the drug into an amorphous form makes it thermodynamically unstable
and thus susceptible to re-crystallisation on storage.
Hot Melt Extrusion Process Parameters
- Temperature,
- Mixing time,
- Feed-rate,
- Pressure, and
- Size and shape of die
CQA of Hot Melt Extrusion Process
Advantages and Disadvantages of Hot-Melt Extrusion (HME)
Advantages
(i) Suitable for low soluble or
insoluble API
(ii) Solvent-free operation
(iii) Automated process
(iv) Reproducible
Disadvantages
(i) Chance of thermal degradation of
sensitive materials
(ii) Non-traditional equipment, specialized
knowledge is required
(iii) Proper carrier selection is
critical
