Rheology of Cellulose Ether Excipients Designed for Hot Melt Extrusion

Biomacromolecules. 2018 Nov 12;19(11):4430-4441. doi: 10.1021/acs.biomac.8b01306. Epub 2018 Oct 24.

Abstract

A new family of cellulosic ether polymeric excipients has been recently engineered for fabrication of amorphous solid dispersions of active pharmaceutical ingredients via hot-melt extrusion (HME). These hydroxypropyl methyl cellulose excipients enable plasticizer-free melt processing at much lower temperatures (135-160 °C) due to their substantially reduced glass transition temperatures ( Tg = 98-110 °C). The novel amorphous cellulose ethers were found to be rheologically solidlike well above their glass transition ( Tg + 70 °C). We demonstrate that in the pharmaceutically relevant HME processing temperature range these polymers behave similarly to yield-stress fluids and flow only when the applied stress exceeds a critical stress value. This critical stress value (0.50 ± 0.05 MPa, 150 °C) is surprisingly high but is easily achieved under typical HME conditions. The origin of their yield-stress fluidlike behavior is hypothesized to arise from hydrogen bonds of the HPMC materials that act as physical cross-links and do not relax within the measured temperature and time window unless the applied stress exceeds the critical stress value. Support for this hypothesis arises from infrared spectroscopic estimates of the free and bound hydrogen bond levels at end-use temperatures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellulose / chemistry*
  • Drug Carriers / chemistry*
  • Ether / chemistry*
  • Excipients / chemistry*
  • Hot Temperature*
  • Pharmaceutical Preparations / chemistry
  • Plasticizers / chemistry*
  • Polymers / chemistry*
  • Rheology

Substances

  • Drug Carriers
  • Excipients
  • Pharmaceutical Preparations
  • Plasticizers
  • Polymers
  • Ether
  • Cellulose