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

Research output: Contribution to journalArticle

4 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
Pages (from-to)192-199
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume132
DOIs
Publication statusPublished - 01-11-2018

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

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