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.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI:10.1007/s11095-025-03852-0

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

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Abstract

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 (K_b) were derived from Benesi-Hildebrand plots. Partition coefficients (K_x) and Gibbs energies (ΔG_x) 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 K_x (81386.259 with P188), attributed to electrostatic interactions and micelle stabilization. SC showed moderate K_x, 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_x < 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.

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波洛沙姆188和波洛沙姆407对酮洛芬（探针分子）与胆酸钠、十二烷基三甲基溴化铵和BrijC10表面活性剂结合系数（单分子）和分配系数（胶束）的影响

酮洛芬是生物制药分类系统（BCS） II类药物，其水溶性较差，需要采用增溶策略才能有效给药。表面活性剂和poloxamers通常通过胶束包封和主客体相互作用来增强增溶作用。目的：研究酮洛芬与表面活性剂胆酸钠（SC）、十二烷基三甲基溴化铵（DTAB）和Brij C10 （BC10）的结合相互作用、化学计量学和分配行为，并考察了poloxam188 （P188）和poloxam407 （P407）作为改性剂的影响。材料和方法：络合化学计量学采用Job图，结合常数（Kb）采用Benesi-Hildebrand图。分配系数（Kx）和吉布斯能（ΔGx）由Kawamura方程确定。测量在25°C恒定酮洛芬浓度下进行。结果与讨论：除了DTAB + P407的比例为1.67:1外，大多数体系的配位比例为1:1。DTAB显示出最高的Kx (81386.259, P188)，这归因于静电相互作用和胶束稳定。SC表现出适度的Kx，由于竞争氢键而被poloxamers还原。BC10，效率最低的增溶剂，通过使胶束核心分配，稍微改善了poloxamers。结论：DTAB，特别是P188，显示出酮洛芬溶解的最大潜力，为设计基于表面活性剂的药物传递系统提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.