Sha'at Mousa, Ochiuz Lacramioara, Rusu Cristina Marcela, Agop Maricel, Barsan Bujor Alexandra, Cretan Monica Stamate, Hartan Mihaela, Spac Adrian Florin
Department of Pharmaceutical Technology, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universității Street, 700115 Iasi, Romania.
Department of Physics, "Gheorghe Asachi" Technical University of Iasi, Prof. Dr. Docent Dimitrie Mangeron Rd., No. 59A, 700050 Iasi, Romania.
Pharmaceutics. 2024 Dec 14;16(12):1595. doi: 10.3390/pharmaceutics16121595.
Diabetes is a growing global health crisis that requires effective therapeutic strategies to optimize treatment outcomes. This study aims to address this challenge by developing and characterizing extended-release polymeric matrix tablets containing metformin hydrochloride (M-HCl), a first-line treatment for type 2 diabetes, and honokiol (HNK), a bioactive compound with potential therapeutic benefits. The objective is to enhance glycemic control and overall therapeutic outcomes through an innovative dual-drug delivery system. The tablets were formulated using hydrophilic polymers, such as Carbopol 71G NF and Noveon AA-1. The release kinetics of M-HCl and HNK were investigated through advanced mathematical models, including fractal and multifractal dynamics, to capture the non-linear and time-dependent release processes. Traditional kinetic models (zero-order, first-order, Higuchi equations) were also evaluated for comparison. In vitro dissolution studies were conducted to determine the release profiles of the active ingredients under varying polymer concentrations. The study revealed distinct release profiles for the two active ingredients. M-HCl exhibited a rapid release phase, with 80% of the drug released within 4-7 h depending on polymer concentration. In contrast, HNK demonstrated a slower release profile, achieving 80% release after 9-10 h, indicating a greater sensitivity to polymer concentration. At shorter intervals, drug release followed classical kinetic models, while multifractal dynamics dominated at longer intervals. Higher polymer concentrations resulted in slower drug release rates due to the formation of a gel-like structure upon hydration, which hindered drug diffusion. The mechanical properties and stability of the matrix tablets confirmed their suitability for extended-release applications. Mathematical modeling validated the experimental findings and provided insights into the structural and time-dependent factors influencing drug release. This study successfully developed dual-drug extended-release matrix tablets containing metformin hydrochloride and honokiol, highlighting the potential of hydrophilic polymers to regulate drug release. The findings emphasize the utility of advanced mathematical models for predicting release kinetics and underscore the potential of these formulations to improve patient compliance and therapeutic outcomes in diabetes management.
糖尿病是一个日益严重的全球健康危机,需要有效的治疗策略来优化治疗效果。本研究旨在通过开发和表征含有盐酸二甲双胍(M-HCl,2型糖尿病的一线治疗药物)和厚朴酚(HNK,一种具有潜在治疗益处的生物活性化合物)的缓释聚合物基质片剂来应对这一挑战。目标是通过创新的双药递送系统增强血糖控制和整体治疗效果。这些片剂使用亲水性聚合物(如卡波姆71G NF和诺维隆AA-1)进行配方设计。通过包括分形和多重分形动力学在内的先进数学模型研究了M-HCl和HNK的释放动力学,以捕捉非线性和时间依赖性释放过程。还评估了传统动力学模型(零级、一级、Higuchi方程)以作比较。进行了体外溶出研究,以确定不同聚合物浓度下活性成分的释放曲线。该研究揭示了两种活性成分不同的释放曲线。M-HCl表现出快速释放阶段,根据聚合物浓度,80%的药物在4至7小时内释放。相比之下,HNK表现出较慢的释放曲线,在9至10小时后达到80%的释放,表明对聚合物浓度更敏感。在较短时间间隔内,药物释放遵循经典动力学模型,而在较长时间间隔内多重分形动力学起主导作用。较高的聚合物浓度导致药物释放速率较慢,因为水合后形成凝胶状结构,阻碍了药物扩散。基质片剂的机械性能和稳定性证实了它们适用于缓释应用。数学建模验证了实验结果,并提供了对影响药物释放的结构和时间依赖性因素的见解。本研究成功开发了含有盐酸二甲双胍和厚朴酚的双药缓释基质片剂,突出了亲水性聚合物调节药物释放的潜力。研究结果强调了先进数学模型在预测释放动力学方面的实用性,并强调了这些制剂在改善糖尿病管理中患者依从性和治疗效果方面的潜力。