Madden Stuart, Carrazana Enrique, Rabinowicz Adrian L
Neurelis, Inc., San Diego, CA 92121, USA.
John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
Pharmaceutics. 2023 Aug 10;15(8):2119. doi: 10.3390/pharmaceutics15082119.
Intranasal delivery of drugs offers several potential benefits related to ease of delivery, rapid onset, and patient experience, which may be of particular relevance to patients with central nervous system (CNS) conditions who experience acute events. Intranasal formulations must be adapted to address anatomical and physiological characteristics of the nasal cavity, including restricted dose volume, limited surface area, and barriers to mucosal absorption, in addition to constraints on the absorption window due to mucociliary clearance. Development of an effective formulation may utilize strategies including the addition of excipients to address the physicochemical properties of the drug within the constraints of nasal delivery. Dodecyl maltoside (DDM) and tetradecyl maltoside are alkylsaccharide permeation enhancers with well-established safety profiles, and studies have demonstrated transiently improved absorption and favorable bioavailability of several compounds in preclinical and clinical trials. Dodecyl maltoside is a component of three US Food and Drug Administration (FDA)-approved intranasal medications: diazepam for the treatment of seizure cluster in epilepsy, nalmefene for the treatment of acute opioid overdose, and sumatriptan for the treatment of migraine. Another drug product with DDM as an excipient is currently under FDA review, and numerous investigational drugs are in early-stage development. Here, we review factors related to the delivery of intranasal drugs and the role of alkylsaccharide permeation enhancers in the context of approved and future intranasal formulations of drugs for CNS conditions.
经鼻给药具有与给药便利性、起效迅速和患者体验相关的若干潜在益处，这对于经历急性事件的中枢神经系统（CNS）疾病患者可能尤为重要。除了由于黏液纤毛清除对吸收窗口的限制外，鼻内制剂还必须进行调整，以适应鼻腔的解剖和生理特征，包括剂量体积受限、表面积有限以及黏膜吸收的障碍。开发有效的制剂可采用多种策略，包括在鼻内给药的限制条件下添加辅料以解决药物的物理化学性质问题。十二烷基麦芽糖苷（DDM）和十四烷基麦芽糖苷是具有良好安全记录的烷基糖渗透促进剂，研究表明，在临床前和临床试验中，几种化合物的吸收得到了短暂改善，生物利用度良好。十二烷基麦芽糖苷是美国食品药品监督管理局（FDA）批准的三种鼻内用药的成分：用于治疗癫痫丛集性发作的地西泮、用于治疗急性阿片类药物过量的纳美芬以及用于治疗偏头痛的舒马曲坦。另一种以DDM为辅料的药品目前正在接受FDA审查，许多研究性药物正处于早期开发阶段。在此，我们综述了与鼻内药物给药相关的因素，以及烷基糖渗透促进剂在已批准的和未来用于中枢神经系统疾病的鼻内药物制剂中的作用。
