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

Ina Petry, Korbinian Löbmann, Holger Grohganz, Thomas Rades, Claudia S. Leopold*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume133
Pages (from-to)151-160
Number of pages10
ISSN0939-6411
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Arginine
  • Co-amorphous
  • Eudragit®
  • Furosemide
  • In situ amorphisation
  • Indomethacin

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