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Licensed Unlicensed Requires Authentication Published by De Gruyter December 6, 2019

Improvement of stability and release of (-)-epicatechin by hot melt extrusion

  • Catalina María Álvarez , Laura Restrepo-Uribe ORCID logo , Jorge Andrés López , Omar Augusto Estrada and María del Pilar Noriega EMAIL logo


Besides its poor dissolution in polymers, the stability, and bitterness of (-)-epicatechin present challenges for additional developments. Polymer formulations rich in flavonoids or other antioxidants can be developed by hot melt extrusion (HME) for enhancement of stability, release, and taste masking. The formulations are extruded at a temperature substantially below the melting point of (-)-epicatechin to avoid its degradation. The corresponding compound consists of about 50% wt. of an active nutraceutical ingredient, in this case (-)-epicatechin, and food grade polymers (GRAS: generally recognized as safe). In order to identify possible chemical or physical changes in the formulations, they were characterized using various techniques, such as differential scanning calorimetry, thermogravimetric analysis, polarized optical microscopy, in vitro release profile, sensory analysis, high-performance liquid chromatography, and Fourier transform infrared spectroscopy. The crystallinity of (-)-epicatechin was reduced after melt extrusion, but its chemical structure remained unchanged. The main contribution of this research is to shed light on the preparation of polymeric formulations based on (-)-epicatechin using HME as an encapsulation technique to improve stability, release, and taste masking, which may be scaled up and commercially launched as nutraceutical products.



active ingredient


Aqualon™ EC N7 Pharm


batch melt mixing


differential scanning calorimetry




Ethocel™ Standard 10 Premium


film casting


Fourier transform infrared spectroscopy


hot melt extrusion


high-performance liquid chromatography


Kollidon® SR


Eudragit® L 100


polymer formulations


polymer formulation 1 (50%wt. EC, 30%wt. AN7, 10%wt. KSR, 10%wt. L100)


polymer formulation 2 (50%wt. EC, 30%wt. ES10, 10%wt. KSR, 10%wt. L100)


polymer formulation 1 processed by batch melt mixer


polymer formulation 2 processed by batch melt mixer


polymer formulation 1 processed by hot melt extrusion


polymer formulation 1 in physical mixture


physical mixture


polarized light optical microscopy


thermal gravimetric analysis


glass transition temperature


melting point


Melt Temperature


heat of fusion


The authors would like to thank for the technical support of the professionals from the Instituto de Capacitación e Investigación del Plástico y del Caucho – ICIPC. Charlie Martin and Leistritz are acknowledged for the loan of a pharmaceutical twin screw extruder (Nano 16). Ashland, DOW, BASF, and EVONIK are gratefully acknowledged for the donation of polymeric excipients. The authors acknowledge the use of the services and infrastructure of Universidad EAFIT, Universidad de Antioquia, and ICIPC. Universidad EAFIT is gratefully acknowledged by the 50% grant of Chem. Catalina Álvarez in the Master in Engineering Program.

  1. Funding: The authors acknowledge the financial support of Colciencias, ICIPC, Vidarium, and Compañía Nacional de Chocolates. Departamento Administrativo de Ciencia, Tecnología e Innovación, funder id:, grant number: FP44842-240-2016.

  2. Conflict of interest statement: The authors declare no conflict of interests.


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Received: 2019-04-25
Accepted: 2019-10-13
Published Online: 2019-12-06
Published in Print: 2019-12-18

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