Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization.
Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization.
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DOI：
10.3390/molecules26247538
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发表时间：
2021-12-13
期刊：
影响因子：
--
通讯作者：
Puchchakayala G
中科院分区：
文献类型：
--
作者：
Dudhipala N;Ettireddy S;Youssef AAA;Puchchakayala G
厄贝沙坦(IR)是一种血管紧张素II受体拮抗剂，具有抗高血压活性。由于低溶解度和首过代谢，IR的生物利用度受到限制。本研究旨在设计、开发和表征环糊精(S)(CD)络合IR(IR-CD)固体脂质纳米粒(IR-CD-SLNS)，以增强其溶解性和缓释行为，并随后通过口服提高生物利用度。在相溶解度研究的基础上，采用凝聚-冷冻干燥法制备了固体包合物，并对其药物含量、包合效率、溶解度和体外溶出度进行了表征。Ir-Cd包合物提高了Ir的溶解度和溶解速度。羟丙基-β-CD(HP-β-CD)包合物的溶出效率明显高于β-CD(β-CD)。将IR/HP-βCD包合物与单硬脂酸甘油酯(GMS)负载到Dyasan112中，采用热均质结合超声法制备SLN。对SLN的理化性质、体外释放度、差示扫描量热法(DSC)、粉末X射线衍射法(PXRD)和室温物理稳定性进行了2个月的评价。微球的粒径为257.6±5.1 nm，多分散指数为0.21±0.03，−为30.5±4.1 mV，含量为99.8±2.5，包封率为93.7±2.5%。与IR-CD包合物相比，IR-CD-SLN和IR-SLN分散体具有较好的缓释作用。差示扫描量热仪(DSC)的测试结果与X射线衍射仪的测试结果相吻合，没有红外吸收峰。优化的IR-CD络合物、IR-SLN和IR-CD-SLN处方在室温下稳定两个月。因此，目前的IR口服制剂可能会显示出更好的口服生物利用度和更长的降压活性，这可能会改善治疗高血压和心力衰竭的疗效。
Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure.
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DOI：
10.1080/21691401.2018.1465068
发表时间：
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影响因子：
5.8
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