Cargando…

Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate

The aim of this research was the production of extrudates for the treatment of hypertension and heart failure and the investigation of the degradation of the peptidomimetic drug enalapril maleate (EM) during hot-melt extrusion (HME). A fast HPLC method was developed to quantify enalapril maleate and...

Descripción completa

Detalles Bibliográficos
Autores principales: Hoffmann, Lena, Breitkreutz, Jörg, Quodbach, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608079/
https://www.ncbi.nlm.nih.gov/pubmed/36297525
http://dx.doi.org/10.3390/pharmaceutics14102091
_version_ 1784818696941731840
author Hoffmann, Lena
Breitkreutz, Jörg
Quodbach, Julian
author_facet Hoffmann, Lena
Breitkreutz, Jörg
Quodbach, Julian
author_sort Hoffmann, Lena
collection PubMed
description The aim of this research was the production of extrudates for the treatment of hypertension and heart failure and the investigation of the degradation of the peptidomimetic drug enalapril maleate (EM) during hot-melt extrusion (HME). A fast HPLC method was developed to quantify enalapril maleate and possible degradation products. Screening experiments revealed that the diketopiperazine derivative (Impurity D) was the main degradation product. Hot-melt extrusion of enalapril maleate with the polymer Soluplus(®) enabled extrusion at 100 °C, whereas a formulation with the polymer Eudragit(®) E PO could be extruded at only 70 °C. Extrusion at 70 °C prevented thermal degradation. A stabilizing molecular interaction between enalapril maleate and Eudragit(®) E PO was identified via FT-IR spectroscopy. Dissolution studies were carried out to study the influence of the formulation on the dissolution behavior of enalapril maleate. These promising results can be transferred to other thermo-sensitive and peptidomimetic drugs to produce extrudates which can be used, for instance, as feedstock material for the production of patient-specific dosage forms via Fused Deposition Modeling (FDM) 3D printing.
format Online
Article
Text
id pubmed-9608079
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96080792022-10-28 Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate Hoffmann, Lena Breitkreutz, Jörg Quodbach, Julian Pharmaceutics Article The aim of this research was the production of extrudates for the treatment of hypertension and heart failure and the investigation of the degradation of the peptidomimetic drug enalapril maleate (EM) during hot-melt extrusion (HME). A fast HPLC method was developed to quantify enalapril maleate and possible degradation products. Screening experiments revealed that the diketopiperazine derivative (Impurity D) was the main degradation product. Hot-melt extrusion of enalapril maleate with the polymer Soluplus(®) enabled extrusion at 100 °C, whereas a formulation with the polymer Eudragit(®) E PO could be extruded at only 70 °C. Extrusion at 70 °C prevented thermal degradation. A stabilizing molecular interaction between enalapril maleate and Eudragit(®) E PO was identified via FT-IR spectroscopy. Dissolution studies were carried out to study the influence of the formulation on the dissolution behavior of enalapril maleate. These promising results can be transferred to other thermo-sensitive and peptidomimetic drugs to produce extrudates which can be used, for instance, as feedstock material for the production of patient-specific dosage forms via Fused Deposition Modeling (FDM) 3D printing. MDPI 2022-09-30 /pmc/articles/PMC9608079/ /pubmed/36297525 http://dx.doi.org/10.3390/pharmaceutics14102091 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hoffmann, Lena
Breitkreutz, Jörg
Quodbach, Julian
Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title_full Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title_fullStr Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title_full_unstemmed Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title_short Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate
title_sort hot-melt extrusion of the thermo-sensitive peptidomimetic drug enalapril maleate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608079/
https://www.ncbi.nlm.nih.gov/pubmed/36297525
http://dx.doi.org/10.3390/pharmaceutics14102091
work_keys_str_mv AT hoffmannlena hotmeltextrusionofthethermosensitivepeptidomimeticdrugenalaprilmaleate
AT breitkreutzjorg hotmeltextrusionofthethermosensitivepeptidomimeticdrugenalaprilmaleate
AT quodbachjulian hotmeltextrusionofthethermosensitivepeptidomimeticdrugenalaprilmaleate