Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers.
Stuart MaddenEnrique CarrazanaAdrian L RabinowiczPublished in: Pharmaceutics (2023)
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.
Keyphrases
- drug induced
- early stage
- drug administration
- clinical trial
- squamous cell carcinoma
- liver failure
- blood brain barrier
- risk assessment
- respiratory failure
- mesenchymal stem cells
- combination therapy
- radiation therapy
- hepatitis b virus
- lymph node
- phase ii
- human health
- open label
- acute respiratory distress syndrome
- aortic dissection
- cell therapy
- electronic health record
- smoking cessation
- locally advanced
- quantum dots
- mechanical ventilation
- chronic rhinosinusitis
- temporal lobe epilepsy