Factors influencing drug deposition in the
nasal cavity upon delivery via nasal sprays

Gao, Mingyue; Shen, Xiu; Mao, Shirui

doi:10.1007/s40005-020-00482-z

Cited by 65 publications

(41 citation statements)

References 52 publications

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“…Other factors that can influence the efficiency of nasal delivery besides the location of drug deposition within the nose include physiochemical properties of the active pharmaceutical ingredient (API; e.g., molecular size, lipophilicity/polarity/ionic charge, enzymatic degradation in the nose), as well as properties of its formulation (e.g., dry powder, liquid, concentration, pH, osmolarity, viscosity) [58]. Just as device factors (e.g., spray pattern, plume geometry, dose volume, droplet size distribution, velocity) can influence where in the nose the drug is deposited, formulation strategies (e.g., enzyme inhibitors, permeation enhancers, particulate design) can also influence uptake across the nasal mucosa [58,59].…”

Section: Additional Factors That May Impact Nasal Drug Deliverymentioning

confidence: 99%

Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Martin

Hoekman

Aurora

et al. 2021

JCM

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The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.

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Section: Additional Factors That May Impact Nasal Drug Deliverymentioning

confidence: 99%

Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Martin

Hoekman

Aurora

et al. 2021

JCM

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“…Dose volume of the sprays is also related to the nasal deposition of the formulation. Generally, the dose volume on the market is 50 μL to 100 μL [ 82 , 83 ] and volumes larger than 100 μL are known to run down the posterior pharynx [ 83 ].…”

Section: Therapeutic Considerations and Delivery Devicesmentioning

confidence: 99%

“…In addition, the spray pattern, droplet size distribution and viscosity of the formulation all influence the nasal deposition and thus the delivery to the brain. Nasal spray pattern is largely influenced by the formulation of the compound, and it is speculated that a narrow plume angle might enable the spray to penetrate deeper into the nasal cavity and result in large deposition area [ 82 ]. In addition, droplet size influences nasal deposition, where larger droplets tend to deposit at the anterior area, whereas smaller droplets deposit in the inner area of the nasal cavity [ 82 ].…”

Section: Therapeutic Considerations and Delivery Devicesmentioning

confidence: 99%

“…Nasal spray pattern is largely influenced by the formulation of the compound, and it is speculated that a narrow plume angle might enable the spray to penetrate deeper into the nasal cavity and result in large deposition area [ 82 ]. In addition, droplet size influences nasal deposition, where larger droplets tend to deposit at the anterior area, whereas smaller droplets deposit in the inner area of the nasal cavity [ 82 ]. Physiological properties such as viscosity of the formulation influence the droplet size of the nasal spray.…”

Section: Therapeutic Considerations and Delivery Devicesmentioning

confidence: 99%

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Intranasal Administration for Pain: Oxytocin and Other Polypeptides

et al. 2021

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Pain, particularly chronic pain, remains one of the most debilitating and difficult-to-treat conditions in medicine. Chronic pain is difficult to treat, in part because it is associated with plastic changes in the peripheral and central nervous systems. Polypeptides are linear organic polymers that are highly selective molecules for neurotransmitter and other nervous system receptors sites, including those associated with pain and analgesia, and so have tremendous potential in pain therapeutics. However, delivery of polypeptides to the nervous system is largely limited due to rapid degradation within the peripheral circulation as well as the blood–brain barrier. One strategy that has been shown to be successful in nervous system deposition of polypeptides is intranasal (IN) delivery. In this narrative review, we discuss the delivery of polypeptides to the peripheral and central nervous systems following IN administration. We briefly discuss the mechanism of delivery via the nasal–cerebral pathway. We review recent studies that demonstrate that polypeptides such as oxytocin, delivered IN, not only reach key pain-modulating regions in the nervous system but, in doing so, evoke significant analgesic effects. IN administration of polypeptides has tremendous potential to provide a non-invasive, rapid and effective method of delivery to the nervous system for chronic pain treatment and management.

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“…To develop a suitable NTBDD system, challenges in nasal drug delivery have to be addressed, some of which are formulation- and device-related, while others are physiological constraints that determine drug retention and permeation in the nasal cavity [ 28 , 29 , 30 ]. For instance, limited nasal residence time due to mucociliary clearance requires the use of non-harmful excipients in nasal formulations, e.g., adsorption enhancers and mucoadhesive agents [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery

2021

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The nasal cavity is an attractive route for both local and systemic drug delivery and holds great potential for access to the brain via the olfactory region, an area where the blood–brain barrier (BBB) is effectively absent. However, the olfactory region is located at the roof of the nasal cavity and only represents ~5–7% of the epithelial surface area, presenting significant challenges for the deposition of drug molecules for nose to brain drug delivery (NTBDD). Aerosolized particles have the potential to be directed to the olfactory region, but their specific deposition within this area is confounded by a complex combination of factors, which include the properties of the formulation, the delivery device and how it is used, and differences in inter-patient physiology. In this review, an in-depth examination of these different factors is provided in relation to both in vitro and in vivo studies and how advances in the fabrication of nasal cast models and analysis of aerosol deposition can be utilized to predict in vivo outcomes more accurately. The challenges faced in assessing the nasal deposition of aerosolized particles within the paediatric population are specifically considered, representing an unmet need for nasal and NTBDD to treat CNS disorders.

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Factors influencing drug deposition in the nasal cavity upon delivery via nasal sprays

Cited by 65 publications

References 52 publications

Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Intranasal Administration for Pain: Oxytocin and Other Polypeptides

In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery

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