Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy. / Ueda, Hiroshi; Peter Bøtker, Johan; Edinger, Magnus; Löbmann, Korbinian; Grohganz, Holger; Müllertz, Anette; Rades, Thomas; Østergaard, Jesper.

In: International Journal of Pharmaceutics, Vol. 587, 119662, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ueda, H, Peter Bøtker, J, Edinger, M, Löbmann, K, Grohganz, H, Müllertz, A, Rades, T & Østergaard, J 2020, 'Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy', International Journal of Pharmaceutics, vol. 587, 119662. https://doi.org/10.1016/j.ijpharm.2020.119662

APA

Ueda, H., Peter Bøtker, J., Edinger, M., Löbmann, K., Grohganz, H., Müllertz, A., Rades, T., & Østergaard, J. (2020). Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy. International Journal of Pharmaceutics, 587, [119662]. https://doi.org/10.1016/j.ijpharm.2020.119662

Vancouver

Ueda H, Peter Bøtker J, Edinger M, Löbmann K, Grohganz H, Müllertz A et al. Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy. International Journal of Pharmaceutics. 2020;587. 119662. https://doi.org/10.1016/j.ijpharm.2020.119662

Author

Ueda, Hiroshi ; Peter Bøtker, Johan ; Edinger, Magnus ; Löbmann, Korbinian ; Grohganz, Holger ; Müllertz, Anette ; Rades, Thomas ; Østergaard, Jesper. / Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy. In: International Journal of Pharmaceutics. 2020 ; Vol. 587.

Bibtex

@article{1359a3cd669b41688581c5f917f2c0e3,
title = "Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy",
abstract = "Co-amorphous systems comprising low-molecular weight drugs and co-formers constitute an interesting approach to optimize pharmaceutical performance of drugs with low aqueous solubility. Within the different types of co-amorphous systems, the combination of a drug with its own salt may be an attractive formulation option due the absence of any inactive co-formers. The aim of this study was to investigate the possibility of forming a co-amorphous system from naproxen (NAP) and its sodium salt (NAP(Na)). Ball milling of NAP and NAP(Na) at equal molar ratio resulted in the formation of a co-amorphous system whilst NAP and NAP(Na) alone were crystalline following both, ball milling and melt quenching. Infrared spectroscopy and physical stability testing revealed that intermolecular interactions were able to maintain the ball milled NAP-NAP(Na) system amorphous for 2 months at 40 °C. Surprisingly, the dissolution rate of co-amorphous NAP-NAP(Na) was only intermediate between those of crystalline NAP and crystalline NAP(Na). In situ Raman spectroscopic measurements indicated an initial phase separation of the co-amorphous form to NAP and NAP(Na) followed by dissociation of sodium from NAP(Na) and crystallization to NAP. These findings contribute to the design of co-amorphous formulations with the combination of a drug and its own salt.",
keywords = "Amorphous, Co-amorphous, Crystallization, Dissolution, Naproxen, Raman spectroscopy, UV imaging",
author = "Hiroshi Ueda and {Peter B{\o}tker}, Johan and Magnus Edinger and Korbinian L{\"o}bmann and Holger Grohganz and Anette M{\"u}llertz and Thomas Rades and Jesper {\O}stergaard",
year = "2020",
doi = "10.1016/j.ijpharm.2020.119662",
language = "English",
volume = "587",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Formulation of co-amorphous systems from naproxen and naproxen sodium and in situ monitoring of physicochemical state changes during dissolution testing by Raman spectroscopy

AU - Ueda, Hiroshi

AU - Peter Bøtker, Johan

AU - Edinger, Magnus

AU - Löbmann, Korbinian

AU - Grohganz, Holger

AU - Müllertz, Anette

AU - Rades, Thomas

AU - Østergaard, Jesper

PY - 2020

Y1 - 2020

N2 - Co-amorphous systems comprising low-molecular weight drugs and co-formers constitute an interesting approach to optimize pharmaceutical performance of drugs with low aqueous solubility. Within the different types of co-amorphous systems, the combination of a drug with its own salt may be an attractive formulation option due the absence of any inactive co-formers. The aim of this study was to investigate the possibility of forming a co-amorphous system from naproxen (NAP) and its sodium salt (NAP(Na)). Ball milling of NAP and NAP(Na) at equal molar ratio resulted in the formation of a co-amorphous system whilst NAP and NAP(Na) alone were crystalline following both, ball milling and melt quenching. Infrared spectroscopy and physical stability testing revealed that intermolecular interactions were able to maintain the ball milled NAP-NAP(Na) system amorphous for 2 months at 40 °C. Surprisingly, the dissolution rate of co-amorphous NAP-NAP(Na) was only intermediate between those of crystalline NAP and crystalline NAP(Na). In situ Raman spectroscopic measurements indicated an initial phase separation of the co-amorphous form to NAP and NAP(Na) followed by dissociation of sodium from NAP(Na) and crystallization to NAP. These findings contribute to the design of co-amorphous formulations with the combination of a drug and its own salt.

AB - Co-amorphous systems comprising low-molecular weight drugs and co-formers constitute an interesting approach to optimize pharmaceutical performance of drugs with low aqueous solubility. Within the different types of co-amorphous systems, the combination of a drug with its own salt may be an attractive formulation option due the absence of any inactive co-formers. The aim of this study was to investigate the possibility of forming a co-amorphous system from naproxen (NAP) and its sodium salt (NAP(Na)). Ball milling of NAP and NAP(Na) at equal molar ratio resulted in the formation of a co-amorphous system whilst NAP and NAP(Na) alone were crystalline following both, ball milling and melt quenching. Infrared spectroscopy and physical stability testing revealed that intermolecular interactions were able to maintain the ball milled NAP-NAP(Na) system amorphous for 2 months at 40 °C. Surprisingly, the dissolution rate of co-amorphous NAP-NAP(Na) was only intermediate between those of crystalline NAP and crystalline NAP(Na). In situ Raman spectroscopic measurements indicated an initial phase separation of the co-amorphous form to NAP and NAP(Na) followed by dissociation of sodium from NAP(Na) and crystallization to NAP. These findings contribute to the design of co-amorphous formulations with the combination of a drug and its own salt.

KW - Amorphous

KW - Co-amorphous

KW - Crystallization

KW - Dissolution

KW - Naproxen

KW - Raman spectroscopy

KW - UV imaging

UR - http://www.scopus.com/inward/record.url?scp=85088100862&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2020.119662

DO - 10.1016/j.ijpharm.2020.119662

M3 - Journal article

C2 - 32682958

AN - SCOPUS:85088100862

VL - 587

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 119662

ER -

ID: 245232318