Parikh Ankit, Kathawala Krishna, Tan Chun Chuan, Garg Sanjay, Zhou Xin-Fu
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Int J Pharm. 2016 Dec 30;515(1-2):490-500. doi: 10.1016/j.ijpharm.2016.10.052. Epub 2016 Oct 24.
Edaravone (EDR), a strong free radical scavenger, is known for its promising therapeutic potential in oxidative stress (OS) associated diseases, however poor oral bioavailability is the major obstacle in its potential use. Oral liquid dosage form is the most preferred delivery method in paediatric, geriatric and specialised therapies. The present research discusses the development of a Novel Oral Delivery System (NODS) of EDR to enhance oral bioavailability. From preformulation study, solubility, and stability were identified as key challenges and the requirement of an acidic environment and protection against oxidation were found to be critical. The NODS made up of a mixture of Labrasol (LBS) and an acidic aqueous system, was optimized on the basis of solubility and stability study. It can be stored ≤40°C for at least one month. Drug release from NODS was slow, sustained and significantly better as compared to suspension. The significant reduction in metabolism and improvement in permeability across the small intestine were observed with NODS compared to free EDR. The oral pharmacokinetic study showed 571% relative bioavailability with NODS compared to EDR suspension. From the results obtained, NODS is a promising candidate for use in OS associated diseases.
依达拉奉（EDR）是一种强效自由基清除剂，因其在氧化应激（OS）相关疾病中具有潜在的治疗潜力而闻名，然而口服生物利用度差是其潜在应用的主要障碍。口服液体制剂是儿科、老年科和特殊治疗中最优选的给药方式。本研究探讨了一种新型依达拉奉口服给药系统（NODS）的开发，以提高其口服生物利用度。从处方前研究中发现，溶解度和稳定性是关键挑战，并且发现酸性环境的需求和抗氧化保护至关重要。由Labrasol（LBS）和酸性水体系混合物组成的NODS，在溶解度和稳定性研究的基础上进行了优化。它可以在≤40°C下储存至少一个月。与混悬剂相比，NODS的药物释放缓慢、持续且显著更好。与游离依达拉奉相比，NODS观察到代谢显著降低且小肠通透性提高。口服药代动力学研究表明，与依达拉奉混悬剂相比，NODS的相对生物利用度为571%。从获得的结果来看，NODS是用于OS相关疾病的有前景的候选药物。
