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Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations
Molecular complexation with cyclodextrins (CDs) has long been a known process for modifying the physicochemical properties of problematic active pharmaceutical ingredients with poor water solubility. In current times, the focus has been on the solvent-free co-grinding process, which is an industrial...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025016/ https://www.ncbi.nlm.nih.gov/pubmed/35456578 http://dx.doi.org/10.3390/pharmaceutics14040744 |
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author | Kondoros, Balázs Attila Jójárt-Laczkovich, Orsolya Berkesi, Ottó Szabó-Révész, Piroska Csóka, Ildikó Ambrus, Rita Aigner, Zoltán |
author_facet | Kondoros, Balázs Attila Jójárt-Laczkovich, Orsolya Berkesi, Ottó Szabó-Révész, Piroska Csóka, Ildikó Ambrus, Rita Aigner, Zoltán |
author_sort | Kondoros, Balázs Attila |
collection | PubMed |
description | Molecular complexation with cyclodextrins (CDs) has long been a known process for modifying the physicochemical properties of problematic active pharmaceutical ingredients with poor water solubility. In current times, the focus has been on the solvent-free co-grinding process, which is an industrially feasible process qualifying as a green technology. In this study, terbinafine hydrochloride (TER), a low solubility antifungal drug was used as a model drug. This study aimed to prepare co-ground products and follow through the preparation process of the co-grinding method in the case of TER and two amorphous CD derivatives: (2-hydroxypropyl)-β-cyclodextrin (HPBCD); heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB). For this evaluation, the following analytical tools and methods were used: phase solubility studies, differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), hot-stage X-ray powder diffractometry (HOT-XRPD), Fourier-transform infrared (FT-IR), Raman spectroscopy, and Scanning Electron Microscopy (SEM). Furthermore, in vitro characterization (dissolution and diffusion studies) was performed in two kinds of dissolution medium without enzymes. In the XRPD and SEM studies, it was found that the co-grinding of the components resulted in amorphous products. FT-IR and Raman spectroscopies confirmed the formation of an inclusion complex through the unsaturated aliphatic chain of TER and CDs. In vitro characterization suggested better dissolution properties for both CDs and decreased diffusion at higher pH levels in the case of HPBCD. |
format | Online Article Text |
id | pubmed-9025016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90250162022-04-23 Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations Kondoros, Balázs Attila Jójárt-Laczkovich, Orsolya Berkesi, Ottó Szabó-Révész, Piroska Csóka, Ildikó Ambrus, Rita Aigner, Zoltán Pharmaceutics Article Molecular complexation with cyclodextrins (CDs) has long been a known process for modifying the physicochemical properties of problematic active pharmaceutical ingredients with poor water solubility. In current times, the focus has been on the solvent-free co-grinding process, which is an industrially feasible process qualifying as a green technology. In this study, terbinafine hydrochloride (TER), a low solubility antifungal drug was used as a model drug. This study aimed to prepare co-ground products and follow through the preparation process of the co-grinding method in the case of TER and two amorphous CD derivatives: (2-hydroxypropyl)-β-cyclodextrin (HPBCD); heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB). For this evaluation, the following analytical tools and methods were used: phase solubility studies, differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), hot-stage X-ray powder diffractometry (HOT-XRPD), Fourier-transform infrared (FT-IR), Raman spectroscopy, and Scanning Electron Microscopy (SEM). Furthermore, in vitro characterization (dissolution and diffusion studies) was performed in two kinds of dissolution medium without enzymes. In the XRPD and SEM studies, it was found that the co-grinding of the components resulted in amorphous products. FT-IR and Raman spectroscopies confirmed the formation of an inclusion complex through the unsaturated aliphatic chain of TER and CDs. In vitro characterization suggested better dissolution properties for both CDs and decreased diffusion at higher pH levels in the case of HPBCD. MDPI 2022-03-30 /pmc/articles/PMC9025016/ /pubmed/35456578 http://dx.doi.org/10.3390/pharmaceutics14040744 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 Kondoros, Balázs Attila Jójárt-Laczkovich, Orsolya Berkesi, Ottó Szabó-Révész, Piroska Csóka, Ildikó Ambrus, Rita Aigner, Zoltán Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title | Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title_full | Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title_fullStr | Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title_full_unstemmed | Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title_short | Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations |
title_sort | development of solvent-free co-ground method to produce terbinafine hydrochloride cyclodextrin binary systems; structural and in vitro characterizations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025016/ https://www.ncbi.nlm.nih.gov/pubmed/35456578 http://dx.doi.org/10.3390/pharmaceutics14040744 |
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