Biorelevant solubility of poorly soluble drugs: Rivaroxaban, furosemide, papaverine and niflumic acid

Krisztina Takács-Novák, Vera Szoke, Gergely Völgyi, Péter Horváth, Rita Ambrus, Piroska Szabó-Révész

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In this work the biorelevant solubility of four drugs representing different acid-base property, wide range of lipohilicity and low aqueous solubility was studied. The equilibrium solubility of rivaroxaban (non-ionizable), furosemide (acid), papaverine (base) and niflumic acid (ampholyte) was determined in simulated gastric fluid (SGF pH 1.2), in simulated intestinal fluid fasted state (FaSSIF pH 6.5) and fed state (FeSSIF pH 5.0) and their corresponding blank buffers at a temperature of 37°C using saturation shake-flask method. The concentration was measured by optimized HPLC analysis. The solubilizing effect of bile acid/lipid micelles as additive components of biorelevent media (BRM) is expressed with the solubility ratio (SR: SBRM/Sblank buffer) and the food effect was estimated from SFeSSIF/SFaSSIF coefficient. It was revealed that ionization plays primarily role in solubility of compounds which undergo ionization in BRM. The solubilizing effect in FaSSIF was marginal for the neutral compound (rivaroxaban) and for molecules are anionic at pH 6.5 (furosemide and niflumic acid). The higher concentration of solubilizing agents in FeSSIF improved the solubility of papaverine carrying positive charge and niflumic acid being partially zwitterionic at pH 5.0.

Original languageEnglish
Pages (from-to)279-285
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume83
DOIs
Publication statusPublished - Sep 1 2013

Keywords

  • Biorelevant solubility
  • FaSSIF
  • FeSSIF
  • Food effect
  • Saturation shake-flask method
  • Solubilization

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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