Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide Full article

Journal

Molecules
, E-ISSN: 1420-3049

Output data

Year: 2021, Volume: 26, Number: 6, Article number : 1513, Pages count : DOI: 10.3390/molecules26061513

Tags

anti-inflammatory action; bioavailability; complexation; disodium salt of glycyrrhizic acid; hydroxypropyl-β-cyclodextrin; intrinsic solubility; magnesium carbonate; micelles; nimesulide; pharmacokinetics; polysaccharide arabinogalactan; solid pharmaceutical dispersions; supramolecular complexes

Authors

Wei Wei ¹ , Evseenko Veronica I. ² , Khvostov Mikhail V. ^2,3 , Borisov Sergey A. ³ , Tolstikova Tatyana G. ³ , Polyakov Nikolay E. ^2,4 , Dushkin Aleksandr V. ^1,2 , Xu Wenhao ¹ , Min Lu ¹ , Su Wenhao ¹

Affiliations

1	National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China
2	Institute of Solid State Chemistry and Mechanochemistry, 18, Novosibirsk, 630128, Russian Federation
3	N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Lavrentiev Avenue 9, Novosibirsk, 630090, Russian Federation
4	Voevodsky Institute of Chemical Kinetics and Combustion, Institutskaya Str. 3, Novosibirsk, 630090, Russian Federation

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 (Na2GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO3. 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 1H-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, Na2GA, 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 Na2GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.

Wei W. , Evseenko V.I. , Khvostov M.V. , Borisov S.A. , Tolstikova T.G. , Polyakov N.E. , Dushkin A.V. , Xu W. , Min L. , Su W.
Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

Molecules. 2021. V.26. N6. 1513 . DOI: 10.3390/molecules26061513 WOS Scopus РИНЦ

Full text from publisher

Published print:	Mar 10, 2021
Published online:	Mar 10, 2021

Web of science	WOS:000645391400001
Scopus	2-s2.0-85103863246
Elibrary	46768518
OpenAlex	W3134476163