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

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.

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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

T g :

Glass transition temperature

T m :

Melting temperature

USP:

United States Pharmacopoeia

UV:

Ultraviolet

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Acknowledgments

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

Funding

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

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Correspondence to Subin Xiong.

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Yi, S., Wang, J., Lu, Y. et al. Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine–Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems. AAPS PharmSciTech 20, 219 (2019). https://doi.org/10.1208/s12249-019-1435-7

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KEY WORDS

  • cellulose
  • felodipine
  • plasticization
  • controlled release
  • hot melt extrusion