Stamate Cretan Monica, Ochiuz Lacramioara, Ghizdovat Vlad, Molcalut Monica, Agop Maricel, Gafițanu Carmen Anatolia, Barsan Bujor Alexandra, Sha'at Mousa, Stamate Ciprian
Department of Pharmaceutical Technology, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.
Biophysics and Medical Physics Department, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.
Pharmaceutics. 2025 Apr 5;17(4):474. doi: 10.3390/pharmaceutics17040474.
Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen-β-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Tablets were formulated using ketoprofen and ketoprofen-β-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol 971P NF, Kollidon VA 64, and Methocel K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen-β-cyclodextrin complex (2:1), and ketoprofen-β-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug-polymer systems. The inclusion of ketoprofen in the β-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4-7 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9-11 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer-drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment.
类风湿性关节炎是一种慢性自身免疫性疾病，会导致严重残疾，需要改进治疗策略以优化抗炎治疗。本研究旨在通过开发和表征一种含有酮洛芬以及具有增强治疗特性的酮洛芬-β-环糊精复合物的缓释聚合物基质片剂来应对这一挑战。目的是使用一种基于将活性物质包合在环糊精复合物中的新型给药系统来改善炎症管理和治疗效果。片剂采用酮洛芬和酮洛芬-β-环糊精复合物与亲水性聚合物如卡波姆971P NF、聚维酮VA 64和羟丙甲纤维素K4M混合制成。通过共沉淀法获得复合物以提高生物利用度。在人工胃液和肠液中体外研究了酮洛芬、酮洛芬-β-环糊精复合物（2:1）和酮洛芬-β-环糊精复合物（1:1）从片剂中的释放动力学，并建立了药物释放曲线。使用先进的数学模型来描述药物-聚合物系统的非线性行为。证实了酮洛芬包含在β-环糊精复合物中，显示出不同的释放曲线。含有1:1复合物的片剂（K-3 F-3）显示快速释放（4 - 7小时内释放96.2%），而含有游离酮洛芬的片剂（K-1 F-4）在9 - 11小时内释放76%。较高的聚合物浓度由于形成凝胶屏障而减缓了释放。药物工艺和稳定性测试支持它们作为缓释剂型的适用性。一种多重分形建模方法描述了释放动力学，将聚合物-药物基质视为一个复杂系统，释放曲线以分形维数和分辨率的变化为特征。特定的亲水性聚合物组合有效地延长了酮洛芬的释放。通过体外研究和数学建模评估的所开发的基质片剂在改善类风湿性关节炎治疗期间的治疗效果和患者依从性方面显示出前景。
