Cargando…
Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide
Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998760/ https://www.ncbi.nlm.nih.gov/pubmed/33802031 http://dx.doi.org/10.3390/molecules26061513 |
_version_ | 1783670626014199808 |
---|---|
author | Wei, Wei Evseenko, Veronica I. Khvostov, Mikhail V. Borisov, Sergey A. Tolstikova, Tatyana G. Polyakov, Nikolay E. Dushkin, Aleksandr V. Xu, Wenhao Min, Lu Su, Weike |
author_facet | Wei, Wei Evseenko, Veronica I. Khvostov, Mikhail V. Borisov, Sergey A. Tolstikova, Tatyana G. Polyakov, Nikolay E. Dushkin, Aleksandr V. Xu, Wenhao Min, Lu Su, Weike |
author_sort | Wei, Wei |
collection | PubMed |
description | Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na(2)GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO(3). Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by (1)H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na(2)GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na(2)GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM. |
format | Online Article Text |
id | pubmed-7998760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79987602021-03-28 Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide Wei, Wei Evseenko, Veronica I. Khvostov, Mikhail V. Borisov, Sergey A. Tolstikova, Tatyana G. Polyakov, Nikolay E. Dushkin, Aleksandr V. Xu, Wenhao Min, Lu Su, Weike Molecules Article Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na(2)GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO(3). Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by (1)H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na(2)GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na(2)GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM. MDPI 2021-03-10 /pmc/articles/PMC7998760/ /pubmed/33802031 http://dx.doi.org/10.3390/molecules26061513 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wei, Wei Evseenko, Veronica I. Khvostov, Mikhail V. Borisov, Sergey A. Tolstikova, Tatyana G. Polyakov, Nikolay E. Dushkin, Aleksandr V. Xu, Wenhao Min, Lu Su, Weike Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title | Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title_full | Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title_fullStr | Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title_full_unstemmed | Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title_short | Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide |
title_sort | solubility, permeability, anti-inflammatory action and in vivo pharmacokinetic properties of several mechanochemically obtained pharmaceutical solid dispersions of nimesulide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998760/ https://www.ncbi.nlm.nih.gov/pubmed/33802031 http://dx.doi.org/10.3390/molecules26061513 |
work_keys_str_mv | AT weiwei solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT evseenkoveronicai solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT khvostovmikhailv solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT borisovsergeya solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT tolstikovatatyanag solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT polyakovnikolaye solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT dushkinaleksandrv solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT xuwenhao solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT minlu solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide AT suweike solubilitypermeabilityantiinflammatoryactionandinvivopharmacokineticpropertiesofseveralmechanochemicallyobtainedpharmaceuticalsoliddispersionsofnimesulide |