In vitro and in vivo comparison between crystalline and co-amorphous salts of naproxen-arginine

Georgia Kasten, Lonita Lobo, Swapnil Dengale, Holger Grohganz, Thomas Rades, Korbinian Löbmann*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

36 Citations (Scopus)

Abstract

Liquid-assisted grinding (LAG) and dry ball milling (DBM) have recently been used to obtain different physical forms of drug-amino acid salts with promising dissolution and physical stability properties. In this work, crystalline and co-amorphous naproxen-arginine mixtures were prepared using LAG and DBM, respectively, and compared with regard to their in vitro and in vivo performance. X-ray powder diffraction and Fourier-transformed infrared spectroscopy showed that LAG led to the formation of a crystalline salt, while DBM led to a co-amorphous salt. These results agreed with the differential scanning calorimetry profiles: a melting point of 230 °C was determined for the crystalline salt, while the co-amorphous formulation showed a single glass transition temperature at approx. 92 °C. Both solid state forms of the salt showed increased intrinsic dissolution rates (14.8 and 74.1-fold, respectively) and also higher solubility (25.3 and 29.8-fold, respectively) compared to the pure crystalline drug in vitro. Subsequently, the co-amorphous salt revealed an improved bioavailability in a pharmacokinetic study, showing a 1.5-fold increase in AUC0-t and a 2.15-fold increase in cmax compared to the pure crystalline drug. In contrast, even though showing a better in vitro performance, the crystalline salt interestingly did not show an increase in bioavailability in comparison to pure crystalline naproxen.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume132
Pages (from-to)192-199
Number of pages8
ISSN0939-6411
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Amino acid
  • Co-amorphous formulations
  • Dissolution
  • In vivo
  • Oral bioavailability study
  • Salts

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