(780b) Melt Rheology of Cellulose Ethers Designed for Hot Melt Extrusion

Melt Rheology of Cellulose Ethers Designed for Hot Melt Extrusion

Authors: Tirtha Chatterjee, Kevin O’Donnell, Yongfu Li, Uma
Shrestha, Robert L. Sammler, Shrikant Khot

Formulation of new drug entities is increasingly challenging
due to poor solubility of the drug and limited polymers that can produce
amorphous solid dispersions (ASDs). One of the leading technologies to
manufacture ASDs is hot melt extrusion (HME) in which the solid or melted drug
is mixed with a molten polymeric carrier. In order to be processed, the
polymeric carrier must have adequate melt rheology at temperatures acceptable
for pharmaceutical applications. The AFFINISOL™ cellulosic polymer family has
been engineered to have a melt viscosity that enables their use as excipients
in HME.  

In order to design a successful HME process the formulator
must understand the excipient melt rheology as a function of operating
conditions. In the present study, the melt rheology of AFFINISOL™ HPMC HME (hydroxypropyl
methylcellulose) and HPMCAS HME (hydroxypropyl methylcellulose acetate
succinate) is presented. Traditionally the melt rheology is characterized using
a rotational rheometer, however, this was found to be inadequate for this
family of polymers. To overcome this challenge an alternative method was
adapted allowing rheological analysis directly in line with a twin screw
extruder. This enables analysis under conditions identical to those a
formulator would experience. Melt viscosity of the cellulose ethers was found
to be dependent upon temperature and shear rate with all polymers exhibiting a
power law shear thinning behavior. The rheology of select formulations
containing model active pharmaceutical ingredients will also be presented.

Figure 1: (Left) Rotational rheology of AFFINISOL™ HPMC HME
at 170 °C exhibiting solid like behavior despite ability to extrude at
temperatures well below this and (Right) alternative in-line method
demonstrating melt viscosity as a function of shear rate at 170 °C.