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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

Abstract

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.

KEY WORDS

cellulose felodipine plasticization controlled release hot melt extrusion 

Abbreviations

APIs

Active pharmaceutical ingredients

ASDs

Amorphous solid dispersions

ChP

Chinese Pharmacopoeia

DSC

Differential scanning calorimetry

EDX

Energy-dispersive X-ray microanalysis

FLDP

Felodipine

FT-IR

Fourier transform infrared spectroscopy

HME

Hot melt extrusion

HPC

Hydroxypropyl cellulose

HPMC

Hydroxypropyl methylcellulose

PBS

Phosphate-buffered solution

PEG

Polyethylene glycol

PG

Propylene glycol

PMs

Physical mixtures

RH

Relative humidity

SDS

Sodium dodecyl sulfate

SEM

Scanning electron microscopy

Tg

Glass transition temperature

Tm

Melting temperature

USP

United States Pharmacopoeia

UV

Ultraviolet

Notes

Acknowledgments

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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