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Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers

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PHARMACEUTICS
卷 15, 期 8, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics15082119

关键词

absorption; central nervous system; dodecyl maltoside; intranasal; Intravail; nasal cavity; rescue therapy; route of administration; solubility; tetradecyl maltoside

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Intranasal delivery of drugs provides advantages in ease of use, rapid onset, and patient experience, making it particularly relevant for patients with acute events related to central nervous system (CNS) conditions. Adaptation of intranasal formulations to the nasal cavity's anatomical and physiological characteristics, including limited dose volume, restricted surface area, and mucosal absorption barriers, is crucial. The addition of alkylsaccharide permeation enhancers, such as dodecyl maltoside (DDM), can optimize drug absorption within the constraints of nasal delivery, as demonstrated by FDA-approved intranasal medications for epilepsy, acute opioid overdose, and migraine.
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.

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