背景:不可预测的情况,如血液凝固,深静脉血栓形成,肺栓塞出现在体内,这是死亡的主要原因。此类病症通常在手术后以及用口服抗凝剂治疗后出现。阿哌沙班是一种新型口服抗凝剂,广泛推荐用于通过抑制因子Xa预防和治疗非瓣膜性心房颤动的中风和血凝块。阿哌沙班的logP为2.71,溶解度差,报告的最大生物利用度约为50%。
目标:因此,目前的研究主要集中在溶解度的提高,生物利用度,和阿哌沙班通过固体脂质纳米粒(SLN)的治疗效果。
方法:使用高压均质机使用热均质化方法开发了SLN。药物-脂质相容性研究通过FTIR进行评估,并且使用差示扫描量热法(DSC)进行热分析。在检查脂质的过程中,阿哌沙班的最高溶解度估计在单硬脂酸甘油酯中,因此选择了配方。此外,胶体溶液由聚乙二醇200稳定。通过考虑3个独立因素和2个依赖参数,实现了专家软件设计(版本13,Stat-Ease)的优化分析。SLN上的专利是印度202321053691,美国专利,10,973,798B2,美国专利,美国专利2021/0069121A1,美国专利2022/0151945A1。
结果:Box-Behnken设计与方差分析一起应用,其显示对于依赖性参数例如粒度和包封效率(p值:0.0476和0.0379)小于0.05的p值。优化的批次F10显示167.1nm的粒径,-19.5mVzeta电位,包封率为87.32%。将优化的批次F10冻干并通过扫描电子显微镜(SEM)分析,其显示130nm的粒度。将固体粉末填充到胶囊中用于口服递送。
结论:通过固体脂质纳米粒,用F10-负载的阿哌沙班实现溶解度和生物利用度的显著改善。此外,持续释放曲线还可以最大程度地减少由于血液凝固而发生的未见的并发症。
BACKGROUND: Unpredictable situations such as clotting of blood, deep vein thrombosis, and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%.
OBJECTIVE: Hence, the current research mainly focused on the improvement of solubility, bioavailability, and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN).
METHODS: The SLN was developed using the hot-homogenization method using a high-pressure homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1.
RESULTS: Box-Behnken design was applied along with ANOVA, which showed a p-value less than 0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476 and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential, and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder was filled into the capsule for oral delivery.
CONCLUSIONS: The marked improvement in solubility and bioavailability was achieved with F10- loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes the unseen complications that occur due to the clotting of blood.