In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study

Research output: Contribution to journalJournal articlepeer-review

Standard

In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study. / Petry, Ina; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas; Leopold, Claudia S.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 133, 01.12.2018, p. 151-160.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Petry, I, Löbmann, K, Grohganz, H, Rades, T & Leopold, CS 2018, 'In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study', European Journal of Pharmaceutics and Biopharmaceutics, vol. 133, pp. 151-160. https://doi.org/10.1016/j.ejpb.2018.10.011

APA

Petry, I., Löbmann, K., Grohganz, H., Rades, T., & Leopold, C. S. (2018). In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study. European Journal of Pharmaceutics and Biopharmaceutics, 133, 151-160. https://doi.org/10.1016/j.ejpb.2018.10.011

Vancouver

Petry I, Löbmann K, Grohganz H, Rades T, Leopold CS. In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study. European Journal of Pharmaceutics and Biopharmaceutics. 2018 Dec 1;133:151-160. https://doi.org/10.1016/j.ejpb.2018.10.011

Author

Petry, Ina ; Löbmann, Korbinian ; Grohganz, Holger ; Rades, Thomas ; Leopold, Claudia S. / In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study. In: European Journal of Pharmaceutics and Biopharmaceutics. 2018 ; Vol. 133. pp. 151-160.

Bibtex

@article{ef53ab8db6b140df8f1a0ba26af04f8f,
title = "In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study",
abstract = "The concept of controlled in situ amorphisation of drug/polymer mixtures has been introduced previously with indomethacin-Eudragit{\textregistered} E and naproxen-Eudragit{\textregistered} E compacts. In the present study, the feasibility of in situ amorphisation of a crystalline API with the low molecular weight coformer arginine was investigated. This research was based on a previous study, which showed that a high relative humidity (75% RH) may induce co-amorphisation of indomethacin with arginine. It was assumed that an in situ co-amorphisation may be achieved, if a tablet containing a crystalline acidic API and the basic amino acid arginine, coated with a gastro-resistant but water-permeable coating, is exposed to an acidic medium. To investigate this hypothesis, tablets containing arginine and either indomethacin or furosemide were coated with Eudragit{\textregistered} L. After different time periods of immersion (10, 20, 30, 60, 120 min) in 0.1 M HCl, samples were analysed with respect to their solid state properties by XRPD, FTIR spectroscopy and modulated temperature DSC. In both formulations co-amorphous API-arginine was already detected after 10 min of immersion. The maximum of co-amorphous content was reached after 20 min with both formulations, while longer immersion time periods than 60 min revealed a partial API recrystallisation. In addition, during immersion of the indomethacin-arginine formulation, basic hydrolysis of indomethacin was observed, which could be prevented by addition of citric acid to the tablet formulation. However, this addition also inhibited the co-amorphisation of indomethacin. In this proof-of-principle study it was shown that the concept of in situ co-amorphisation of APIs with arginine might be a feasible formulation approach for those poorly water-soluble drugs, which are not susceptible to basic hydrolysis.",
keywords = "Arginine, Co-amorphous, Eudragit{\textregistered}, Furosemide, In situ amorphisation, Indomethacin",
author = "Ina Petry and Korbinian L{\"o}bmann and Holger Grohganz and Thomas Rades and Leopold, {Claudia S.}",
year = "2018",
month = dec,
day = "1",
doi = "10.1016/j.ejpb.2018.10.011",
language = "English",
volume = "133",
pages = "151--160",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium – A proof of concept study

AU - Petry, Ina

AU - Löbmann, Korbinian

AU - Grohganz, Holger

AU - Rades, Thomas

AU - Leopold, Claudia S.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The concept of controlled in situ amorphisation of drug/polymer mixtures has been introduced previously with indomethacin-Eudragit® E and naproxen-Eudragit® E compacts. In the present study, the feasibility of in situ amorphisation of a crystalline API with the low molecular weight coformer arginine was investigated. This research was based on a previous study, which showed that a high relative humidity (75% RH) may induce co-amorphisation of indomethacin with arginine. It was assumed that an in situ co-amorphisation may be achieved, if a tablet containing a crystalline acidic API and the basic amino acid arginine, coated with a gastro-resistant but water-permeable coating, is exposed to an acidic medium. To investigate this hypothesis, tablets containing arginine and either indomethacin or furosemide were coated with Eudragit® L. After different time periods of immersion (10, 20, 30, 60, 120 min) in 0.1 M HCl, samples were analysed with respect to their solid state properties by XRPD, FTIR spectroscopy and modulated temperature DSC. In both formulations co-amorphous API-arginine was already detected after 10 min of immersion. The maximum of co-amorphous content was reached after 20 min with both formulations, while longer immersion time periods than 60 min revealed a partial API recrystallisation. In addition, during immersion of the indomethacin-arginine formulation, basic hydrolysis of indomethacin was observed, which could be prevented by addition of citric acid to the tablet formulation. However, this addition also inhibited the co-amorphisation of indomethacin. In this proof-of-principle study it was shown that the concept of in situ co-amorphisation of APIs with arginine might be a feasible formulation approach for those poorly water-soluble drugs, which are not susceptible to basic hydrolysis.

AB - The concept of controlled in situ amorphisation of drug/polymer mixtures has been introduced previously with indomethacin-Eudragit® E and naproxen-Eudragit® E compacts. In the present study, the feasibility of in situ amorphisation of a crystalline API with the low molecular weight coformer arginine was investigated. This research was based on a previous study, which showed that a high relative humidity (75% RH) may induce co-amorphisation of indomethacin with arginine. It was assumed that an in situ co-amorphisation may be achieved, if a tablet containing a crystalline acidic API and the basic amino acid arginine, coated with a gastro-resistant but water-permeable coating, is exposed to an acidic medium. To investigate this hypothesis, tablets containing arginine and either indomethacin or furosemide were coated with Eudragit® L. After different time periods of immersion (10, 20, 30, 60, 120 min) in 0.1 M HCl, samples were analysed with respect to their solid state properties by XRPD, FTIR spectroscopy and modulated temperature DSC. In both formulations co-amorphous API-arginine was already detected after 10 min of immersion. The maximum of co-amorphous content was reached after 20 min with both formulations, while longer immersion time periods than 60 min revealed a partial API recrystallisation. In addition, during immersion of the indomethacin-arginine formulation, basic hydrolysis of indomethacin was observed, which could be prevented by addition of citric acid to the tablet formulation. However, this addition also inhibited the co-amorphisation of indomethacin. In this proof-of-principle study it was shown that the concept of in situ co-amorphisation of APIs with arginine might be a feasible formulation approach for those poorly water-soluble drugs, which are not susceptible to basic hydrolysis.

KW - Arginine

KW - Co-amorphous

KW - Eudragit®

KW - Furosemide

KW - In situ amorphisation

KW - Indomethacin

U2 - 10.1016/j.ejpb.2018.10.011

DO - 10.1016/j.ejpb.2018.10.011

M3 - Journal article

C2 - 30339888

AN - SCOPUS:85055117583

VL - 133

SP - 151

EP - 160

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -

ID: 214519949