Sha'at Mousa, Ignat Maria, Doroftei Florica, Ghizdovat Vlad, Agop Maricel, Barsan Bujor Alexandra, Cretan Monica Stamate, Sha'at Fawzia, Pavaloiu Ramona-Daniela, Spac Adrian Florin, Ochiuz Lacramioara, Filip Carmen Nicoleta, Popa Ovidiu
Department of Pharmaceutical Technology, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universității Street, 700115 Iasi, Romania.
Laboratory of Material Chemistry, Department of Chemistry, "Alexandru Ioan Cuza" University of Iasi, Bv. Carol I, No. 11, 700506 Iasi, Romania.
Pharmaceutics. 2025 Jul 4;17(7):882. doi: 10.3390/pharmaceutics17070882.
Mesoporous silica materials, particularly KIT-6, offer promising features, such as large surface area, tunable pore structures, and biocompatibility, making them ideal candidates for advanced drug delivery systems. The aims of this study were to develop and evaluate an innovative modified-release platform for metformin hydrochloride (MTF), using KIT-6 mesoporous silica as a matrix, to enhance oral antidiabetic therapy. KIT-6 was synthesized using an ultrasound-assisted sol-gel method and subsequently loaded with MTF via adsorption from alkaline aqueous solutions at two concentrations (1 and 3 mg/mL). The structural and morphological characteristics of the matrices-before and after drug loading-were assessed using SEM-EDX, TEM, and nitrogen adsorption-desorption isotherms (the BET method). In vitro drug release profiles were recorded in simulated gastric and intestinal fluids over 12 h. Kinetic modeling was performed using seven classical models, and a multifractal theoretical framework was used to further interpret the complex release behavior. The loading efficiency increased with increasing drug concentration but nonlinearly, reaching 56.43 mg/g for 1 mg/mL and 131.69 mg/g for 3 mg/mL. BET analysis confirmed significant reductions in the surface area and pore volume upon MTF incorporation. In vitro dissolution showed a biphasic release: a fast initial phase in an acidic medium followed by sustained release at a neutral pH. The Korsmeyer-Peppas and Weibull models best described the release profiles, indicating a predominantly diffusion-controlled mechanism. The multifractal model supported the experimental findings, capturing nonlinear dynamics, memory effects, and soliton-like transport behavior across resolution scales. The study confirms the potential of KIT-6 as a reliable and efficient carrier for the modified oral delivery of metformin. The combination of experimental and multifractal modeling provides a deeper understanding of drug release mechanisms in mesoporous systems and offers a predictive tool for future drug delivery design. This integrated approach can be extended to other active pharmaceutical ingredients with complex release requirements.
介孔二氧化硅材料，尤其是KIT-6，具有诸如大表面积、可调节的孔结构和生物相容性等有前景的特性，使其成为先进药物递送系统的理想候选材料。本研究的目的是开发并评估一种创新的盐酸二甲双胍（MTF）缓释平台，以KIT-6介孔二氧化硅为基质，增强口服抗糖尿病治疗效果。采用超声辅助溶胶-凝胶法合成KIT-6，随后通过从两种浓度（1和3 mg/mL）的碱性水溶液中吸附来负载MTF。使用扫描电子显微镜-能谱仪（SEM-EDX）、透射电子显微镜（TEM）和氮吸附-脱附等温线（BET法）评估载药前后基质的结构和形态特征。在模拟胃液和肠液中记录12小时的体外药物释放曲线。使用七种经典模型进行动力学建模，并使用多重分形理论框架进一步解释复杂的释放行为。负载效率随药物浓度增加而非线性增加，1 mg/mL时达到56.43 mg/g，3 mg/mL时达到131.69 mg/g。BET分析证实，加入MTF后表面积和孔体积显著减小。体外溶出显示出双相释放：在酸性介质中为快速初始阶段，随后在中性pH下持续释放。Korsmeyer-Peppas模型和Weibull模型最能描述释放曲线，表明主要是扩散控制机制。多重分形模型支持实验结果，捕捉了跨分辨率尺度的非线性动力学、记忆效应和类孤子传输行为。该研究证实了KIT-6作为二甲双胍改良口服递送的可靠且高效载体的潜力。实验和多重分形建模的结合提供了对介孔系统中药物释放机制的更深入理解，并为未来药物递送设计提供了预测工具。这种综合方法可扩展到其他具有复杂释放要求的活性药物成分。
