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

  • Glass transition temperature
  • Melting point
  • HLB value


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