Interlaboratory validation of small-scale solubility and dissolution measurements of poorly water-soluble drugs

Research output: Contribution to journalJournal articleResearchpeer-review

  • Sara B. E. Andersson
  • Caroline Alvebratt
  • Jan Bevernage
  • Damien Bonneau
  • Claudia da Costa Mathews
  • Rikesh Dattani
  • Khadijah Edueng
  • Yan He
  • René Holm
  • Cecilie Maria Madsen
  • Thomas Müller
  • Uwe Muenster
  • Müllertz, Anette
  • Krista Ojala
  • Rades, Thomas
  • Peter Sieger
  • Christel A. S. Bergström

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp >1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Issue number9
Pages (from-to)2864-72
Number of pages9
Publication statusPublished - Sep 2016

    Research areas

  • Journal Article

ID: 169382437