Biorelevant characterisation of amorphous furosemide salt exhibits conversion to a furosemide hydrate during dissolution

Line Hagner Nielsen, Sarah Gordon, Jari Pekka Pajander, Jesper Østergaard, Thomas Rades, Anette Müllertz

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Biorelevant dissolution behaviour of the amorphous sodium salt and amorphous acid forms of furosemide was evaluated, together with investigations of the solid state changes during in vitro dissolution in medium simulating the conditions in the small intestine. UV imaging of the two amorphous forms, as well as of crystalline furosemide salt and acid showed a higher rate of dissolution of the salt forms in comparison with the two acid forms. The measured dissolution rates of the four furosemide forms from the UV imaging system and from eluted effluent samples were consistent with dissolution rates obtained from micro dissolution experiments. Partial least squares-discriminant analysis of Raman spectra of the amorphous acid form during flow through dissolution showed that the amorphous acid exhibited a fast conversion to the crystalline acid. Flow through dissolution coupled with Raman spectroscopy showed a conversion of the amorphous furosemide salt to a more stable polymorph. It was found by thermogravimetric analysis and hot stage microscopy that the salt forms of furosemide converted to a trihydrate during dissolution. It can be concluded that during biorelevant dissolution, the amorphous and crystalline furosemide salt converted to a trihydrate, whereas the amorphous acid exhibited fast conversion to the crystalline acid.

Original languageEnglish
Pages (from-to)14-24
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume457
Issue number1
Early online date16 Sep 2013
DOIs
Publication statusPublished - 30 Nov 2013

Bibliographical note

Funding Information:
The authors would like to acknowledge the Villum Kann Rasmussen Foundation for financial support, together with NAnoMEChanical sensors and actuators, fundamentals and new directions (NAMEC) – a VKR Centre of Excellence. Furthermore, Dr. Kaisa Naelapää is acknowledged for assistance with the Raman flow through setup and optimisation of the testing procedure.

Keywords

  • Amorphous form
  • Biorelevant dissolution
  • Furosemide
  • Raman flow through dissolution
  • Solid state conversion
  • UV imaging

ASJC Scopus subject areas

  • Pharmaceutical Science

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