Melt Rheology of Cellulose Ethers Designed for Hot Melt Extrusion

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. The polymeric carrier must have adequate melt rheology at temperatures acceptable for pharmaceutical applications. The AFFINISOL™ HPMC HME cellulosic polymer family has been engineered to have a melt viscosity that enables their use as excipients in HME. These (AFFINISOL^TM HPMC HME) cellulose ethers were found showing solid-like viscoelasticity well beyond their glass transition (T_g +70 ^oC). We demonstrate that in pharma-relevant HME processing temperature range these polymers behave as yield-stress fluids and flow only when the applied stress exceeds a critical stress value (yield stress) which is easily achieved at typical extrusion conditions. An infrared spectroscopic study revealed that the majority of the hydroxyl groups in cellulose ether chains remain hydrogen-bonded (either intra- or inter-molecular) between 50 and 250 ^oC. We hypothesize that these hydrogen bonds act as physical crosslinks that give rise to yield-stress like rheological properties.