Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state

Research output: Contribution to journalJournal articlepeer-review

Standard

Reaction between drug substances and pharmaceutical excipients : formation of citric acid esters and amides of carvedilol in the solid state. / Larsen, Jesper; Cornett, Claus; Jaroszewski, Jerzy Witold; Hansen, Steen H.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 49, No. 1, 2009, p. 11-17.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Larsen, J, Cornett, C, Jaroszewski, JW & Hansen, SH 2009, 'Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state', Journal of Pharmaceutical and Biomedical Analysis, vol. 49, no. 1, pp. 11-17. https://doi.org/10.1016/j.jpba.2008.09.039

APA

Larsen, J., Cornett, C., Jaroszewski, J. W., & Hansen, S. H. (2009). Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state. Journal of Pharmaceutical and Biomedical Analysis, 49(1), 11-17. https://doi.org/10.1016/j.jpba.2008.09.039

Vancouver

Larsen J, Cornett C, Jaroszewski JW, Hansen SH. Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state. Journal of Pharmaceutical and Biomedical Analysis. 2009;49(1):11-17. https://doi.org/10.1016/j.jpba.2008.09.039

Author

Larsen, Jesper ; Cornett, Claus ; Jaroszewski, Jerzy Witold ; Hansen, Steen H. / Reaction between drug substances and pharmaceutical excipients : formation of citric acid esters and amides of carvedilol in the solid state. In: Journal of Pharmaceutical and Biomedical Analysis. 2009 ; Vol. 49, No. 1. pp. 11-17.

Bibtex

@article{2704faa0eb7d11ddbf70000ea68e967b,
title = "Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state",
abstract = "The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR spectroscopy. Heating a mixture of solid carvedilol and solid citric acid monohydrate for 96h at 50 degrees C resulted in the formation of about 3% of a symmetrical ester as well as of a number of other reaction products in smaller amounts. Formation of the symmetrical ester was also observed at room temperature. At 70 degrees C, the amounts of three isomeric esters formed reached 6-8%. The minor reaction products were citric acid amides, O-acetylcarvedilol, and esters of itaconic acid.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Jesper Larsen and Claus Cornett and Jaroszewski, {Jerzy Witold} and Hansen, {Steen H}",
note = "Keywords: Carvedilol; Citric acid; Solid-state reaction; LC-MS; NMR",
year = "2009",
doi = "10.1016/j.jpba.2008.09.039",
language = "English",
volume = "49",
pages = "11--17",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Reaction between drug substances and pharmaceutical excipients

T2 - formation of citric acid esters and amides of carvedilol in the solid state

AU - Larsen, Jesper

AU - Cornett, Claus

AU - Jaroszewski, Jerzy Witold

AU - Hansen, Steen H

N1 - Keywords: Carvedilol; Citric acid; Solid-state reaction; LC-MS; NMR

PY - 2009

Y1 - 2009

N2 - The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR spectroscopy. Heating a mixture of solid carvedilol and solid citric acid monohydrate for 96h at 50 degrees C resulted in the formation of about 3% of a symmetrical ester as well as of a number of other reaction products in smaller amounts. Formation of the symmetrical ester was also observed at room temperature. At 70 degrees C, the amounts of three isomeric esters formed reached 6-8%. The minor reaction products were citric acid amides, O-acetylcarvedilol, and esters of itaconic acid.

AB - The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR spectroscopy. Heating a mixture of solid carvedilol and solid citric acid monohydrate for 96h at 50 degrees C resulted in the formation of about 3% of a symmetrical ester as well as of a number of other reaction products in smaller amounts. Formation of the symmetrical ester was also observed at room temperature. At 70 degrees C, the amounts of three isomeric esters formed reached 6-8%. The minor reaction products were citric acid amides, O-acetylcarvedilol, and esters of itaconic acid.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.jpba.2008.09.039

DO - 10.1016/j.jpba.2008.09.039

M3 - Journal article

C2 - 18996664

VL - 49

SP - 11

EP - 17

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 1

ER -

ID: 9934907