O'Neill Riuna, Yoo Okhee, Burcham Philip, Lim Lee Yong
Division of Pharmacy, School of Allied Health, University of Western Australia, Perth, WA 6009, Australia.
Institute for Paediatric Perioperative Excellence, University of Western Australia, Perth, WA 6009, Australia.
Pharmaceutics. 2024 Jul 26;16(8):993. doi: 10.3390/pharmaceutics16080993.
Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community.
依达拉奉是治疗运动神经元病（MND）的两种主要药物之一。本综述在评估了导致已获批的静脉注射和口服液体制剂临床应用不佳的问题后，提出了依达拉奉的特定质量目标产品概况（QTPP）。随后，对照QTPP对已发表的专利和期刊文献中描述的依达拉奉替代口服制剂进行了综述。共综述了六个研究小组发表的14篇关于18种用于治疗MND的依达拉奉新型口服制剂的文献。替代口服制剂包括用环糊精、脂质、表面活性剂、助表面活性剂、碱化剂、片剂辅料和共溶剂开发的液体制剂和固体制剂。大多数制剂旨在使依达拉奉在胃肠道下段（GIT）吸收；然而，也有四种制剂旨在实现依达拉奉的口腔黏膜吸收以避免首过代谢。与依达拉奉水悬浮液相比，所有新型制剂均提高了依达拉奉的水溶性、稳定性和口服生物利用度（BA）。已发表制剂的一个共同局限性是缺乏以MND患者为中心的数据。除TW001外，没有其他制剂在MND患者中进行过试验。为满足MND患者口服依达拉奉制剂的QTPP，建议设计一种大小合适、口感和稳定性可接受的片剂，以实现依达拉奉有效的舌下或颊黏膜吸收。该片剂的设计应有MND患者群体的参与。
