Evaluation of the impact of mucin on supersaturation and permeation of BCS class 2 basic drugs

J Pharm Sci. 2024 Nov;113(11):3272-3278. doi: 10.1016/j.xphs.2024.08.016. Epub 2024 Aug 22.

Abstract

This study evaluated the impact of mucin on supersaturation and permeation of BCS Class 2 basic drugs in a pH-shift, 2-stage model using three model compounds, dipyridamole, ricobendazole, and Compound A. The three compounds showed various degrees of supersaturation (DoS) in Stage 2 and modest to no increases in flux with the presence of mucin in the dissolution media. Mucin's impact on DoS and flux, if any, appeared to be compound specific and possibly related to its pKa and ionization state. Overall, the increases in supersaturation and permeation due to mucin ranged from modest to minimal for the three model compounds under the conditions tested. The pH-shift model using MacroFLUX was able to monitor gastric and intestinal dissolution and simultaneously assess the effect of intestinal mucin on supersaturation and flux.

Keywords: MacroFLUX; Mucin; Precipitation; Supersaturation; Two-stage dissolution/permeation.

MeSH terms

  • Animals
  • Biopharmaceutics / methods
  • Dipyridamole / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism
  • Models, Biological
  • Mucins* / chemistry
  • Mucins* / metabolism
  • Permeability
  • Solubility*

Substances

  • Mucins
  • Dipyridamole