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Introduction <p>Ketoprofen, a Biopharmaceutics Classification System (BCS) class II drug, exhibits poor water solubility, necessitating solubilization strategies for effective drug delivery. Surfactants and poloxamers are commonly employed to enhance solubilization via micellar encapsulation and host–guest interactions.</p> Aim <p>This study investigates the binding interactions, stoichiometry, and partitioning behavior of ketoprofen with surfactants—sodium cholate (SC), dodecyltrimethylammonium bromide (DTAB), and Brij C10 (BC10)—and examines the impact of Poloxamer 188 (P188) and Poloxamer 407 (P407) as modifiers.</p> Materials and Methods <p>Complexation stoichiometry was evaluated using Job's plots, while binding constants (K<sub>b</sub>​) were derived from Benesi-Hildebrand plots. Partition coefficients (K<sub>x</sub>) and Gibbs energies (ΔG<sub>x</sub>​) were determined using Kawamura's equation. Measurements were conducted at 25°C with constant ketoprofen concentrations.</p> Results and Discussion <p>Job's plots indicated 1:1 complexation for most systems, except DTAB + P407, which exhibited a 1.67:1 ratio. DTAB displayed the highest K<sub>x</sub> (81386.259 with P188), attributed to electrostatic interactions and micelle stabilization. SC showed moderate K<sub>x</sub>​, reduced by poloxamers due to competitive hydrogen bonding. BC10, the least efficient solubilizer, improved slightly with poloxamers by enabling micellar core partitioning. Gibbs energy (ΔG<sub>x</sub> &lt; 0) confirmed spontaneous solubilization, with the most favorable values for DTAB + P188. Discrepancies between Job's and Benesi-Hildebrand plots highlighted the limitations of the latter for low-CMC surfactants.</p> Conclusion <p>DTAB, particularly with P188, demonstrated the greatest potential for ketoprofen solubilization, providing valuable insights for designing surfactant-based drug delivery systems.</p> Graphical Abstract <p></p>

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A Preformulation Experiment: The Influence of Poloxamer 188 and Poloxamer 407 on the Binding Coefficients (Single Molecule) and the Partitioning Coefficients (Micelle) of Ketoprofen (Probe Molecule) with Sodium Cholate, Dodecyl Trimethylammonium Bromide and BrijC10 Surfactants

  • 期刊论文

  • 发表日期：

    2025年4月4日

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  • Zita Farkaš Agatić,
  • Vesna Tepavčević,
  • Mladena Lalić-Popović,
  • Nemanja Todorović,
  • Ana Stjepanović,
  • Mihalj Poša

摘要

Introduction

Ketoprofen, a Biopharmaceutics Classification System (BCS) class II drug, exhibits poor water solubility, necessitating solubilization strategies for effective drug delivery. Surfactants and poloxamers are commonly employed to enhance solubilization via micellar encapsulation and host–guest interactions.

Aim

This study investigates the binding interactions, stoichiometry, and partitioning behavior of ketoprofen with surfactants—sodium cholate (SC), dodecyltrimethylammonium bromide (DTAB), and Brij C10 (BC10)—and examines the impact of Poloxamer 188 (P188) and Poloxamer 407 (P407) as modifiers.

Materials and Methods

Complexation stoichiometry was evaluated using Job's plots, while binding constants (Kb​) were derived from Benesi-Hildebrand plots. Partition coefficients (Kx) and Gibbs energies (ΔGx​) were determined using Kawamura's equation. Measurements were conducted at 25°C with constant ketoprofen concentrations.

Results and Discussion

Job's plots indicated 1:1 complexation for most systems, except DTAB + P407, which exhibited a 1.67:1 ratio. DTAB displayed the highest Kx (81386.259 with P188), attributed to electrostatic interactions and micelle stabilization. SC showed moderate Kx​, reduced by poloxamers due to competitive hydrogen bonding. BC10, the least efficient solubilizer, improved slightly with poloxamers by enabling micellar core partitioning. Gibbs energy (ΔGx < 0) confirmed spontaneous solubilization, with the most favorable values for DTAB + P188. Discrepancies between Job's and Benesi-Hildebrand plots highlighted the limitations of the latter for low-CMC surfactants.

Conclusion

DTAB, particularly with P188, demonstrated the greatest potential for ketoprofen solubilization, providing valuable insights for designing surfactant-based drug delivery systems.

Graphical Abstract