Investigating the Influence of Mucus Layer, Bile Acids, and Pharmaceutical Excipients on the Intestinal Permeability of Solifenacin Using PermeaPadTM Plate

Abstract

This study investigates the intestinal permeability of solifenacin (SOL), a drug which is reported to have both hydrophilic and hydrophobic interaction with taurocholic acid (TCA), and its commercial formulation using an in vitro method with the PermeaPad^TM plate (PPP) and fasted state simulated intestinal fluid (FaSSIF).

The research addresses the limitations of traditional methods like the parallel artificial membrane permeation assay (PAMPA), which can be damaged by components in the intestinal environment. The findings reveal that SOL interacts with TCA to form a complex that affects its permeability, and that this process is influenced by concentrations of both SOL and TCA, as well as the presence of excipients.

The introduction of a mucus layer in the experimental setup resulted in a significant reduction in SOL permeability, highlighting the complex interactions between the mucus layer, bile acids, and excipients. The study concludes that PPP is a viable alternative to cell-based methods for evaluating drug permeability. This work provides insights into the mechanisms of drug permeability, which is crucial for drug development.

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Materials

PPP was purchased from Phabioc GmbH (Espelkamp, Germany). SOL succinate and 1 mg/mL solifenacin succinate oral suspension (SOL-DP) were supplied by Astellas Pharma Inc (Tokyo, Japan). The SOL-DP contained the following excipients in addition to SOL: polacrilin potassium (adsorbent), methylparaben and propylparaben (antimicrobial preservation), propylene glycol (solubilizer), simethicone emulsion (antifoam agent), Carbopol 974P (thickener), xylitol and acesulfame potassium (sweetener).

Yuki Hagiwara, Kouichi Yoshinari, Investigating the Influence of Mucus Layer, Bile Acids, and Pharmaceutical Excipients on the Intestinal Permeability of Solifenacin Using PermeaPadTM Plate, Journal of Pharmaceutical Sciences, 2025, 103976, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2025.103976.