AAPS PharmSciTech

, 20:219 | Cite as

Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine–Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems

  • Shan Yi
  • Jiandong Wang
  • Yang Lu
  • Ruyu Ma
  • Qi Gao
  • Shulai Liu
  • Subin XiongEmail author
Research Article


Hydroxypropyl methylcellulose (HPMC) is a hydrophilic retarding-release polymer with the limited application in hot melt extrusion (HME) due to its high glass transition temperature (Tg 181–191°C) and melt viscosity. The aim of this study is to develop hot melt extruded matrices using hydroxypropyl cellulose (HPC) and felodipine (FLDP) with HPMC for controlled release and explore the relations of their specialty, processability, and structure with the product properties. Results showed that FLDP/HPCEF/HPMC can be extruded at 160°C with torques not more than 0.5 N·m. The extruded matrices of FLDP/HPCEF/HPMCK15M (10:45:45 and 30:35:35) achieved the controlled release for 24 h. Rheological behaviors demonstrated that HPCEF and FLDP were miscible with HPMCK15M, attaining maximum 30% FLDP soluble in the molten mixtures. HPCEF and FLDP decreased the complex viscosity and plasticized HPMCK15M to improve the extrusion processing. DSC and FT-IR indicated that the molten soluble FLDP was amorphous in the extruded matrices by hydrogen bonding with HPCEF/HPMCK15M. SEM/energy-dispersive X-ray microanalysis illustrated that the microstructure of extrudates was surface dense and interior loose, and FLDP was homogenously dispersed. Three-point bending test revealed that the plasticizers of HPCEF and FLDP contributed differently to the mechanical properties. HPCEF decreased the flexural modulus of HPMCK15M while that of HPCEF/HPMCK15M was increased by FLDP. Besides controlled release, low moisture absorption and enhanced stability were also the correlated achievements. Therefore, HPCEF-combined poorly water-soluble drugs to plasticize HPMCK15M provide an alternative novel potential approach to realize the controlled-release delivery via HME.


cellulose felodipine plasticization controlled release hot melt extrusion 



Active pharmaceutical ingredients


Amorphous solid dispersions


Chinese Pharmacopoeia


Differential scanning calorimetry


Energy-dispersive X-ray microanalysis




Fourier transform infrared spectroscopy


Hot melt extrusion


Hydroxypropyl cellulose


Hydroxypropyl methylcellulose


Phosphate-buffered solution


Polyethylene glycol


Propylene glycol


Physical mixtures


Relative humidity


Sodium dodecyl sulfate


Scanning electron microscopy


Glass transition temperature


Melting temperature


United States Pharmacopoeia





We greatly appreciate the Thermo Fisher Scientific for providing the support of rheological study.

Funding Information

This work was supported by the National Natural Science Foundation of China (No. 30701059) and the Natural Science Foundation of Zhejiang Province (No. LY13H300004).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Shan Yi
    • 1
  • Jiandong Wang
    • 1
  • Yang Lu
    • 1
  • Ruyu Ma
    • 1
  • Qi Gao
    • 1
  • Shulai Liu
    • 2
  • Subin Xiong
    • 1
    Email author
  1. 1.College of Pharmaceutical SciencesZhejiang University of TechnologyHangzhouPeople’s Republic of China
  2. 2.Ocean CollegeZhejiang University of TechnologyHangzhouPeople’s Republic of China

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