Nasal Drug Delivery
Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound and protein drugs, for systemic medication. Drugs are cleared rapidly from the nasal cavity after intra-nasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The advantages of the drug delivery systems applied via the nasal route, which have bio-adhesive properties. The nasal mucosa presents an ideal site for bio-adhesive drug delivery systems. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenteraly. Bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bio-adhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone).
How does nasal delivery work?
Inhalation/pulmonary drug delivery system includes
Merits for Nasal Drug Delivery
Limitations
Pathways for nasal absorption
Therapeutic class of drugs which can be delivered by nasal route
Physiological effects
Properties
API properties
Effect of particle size
Effect of molecular size
Effect of solution pH
Effect of drug lipophilicity
Effect of drug concentration
Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound and protein drugs, for systemic medication. Drugs are cleared rapidly from the nasal cavity after intra-nasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The advantages of the drug delivery systems applied via the nasal route, which have bio-adhesive properties. The nasal mucosa presents an ideal site for bio-adhesive drug delivery systems. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenteraly. Bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bio-adhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone).
How does nasal delivery work?
- Produces a spray of expelled formulation produces a spray of expelled formulation (most of the time liquid), which is directed (most of the time liquid), which is directed into the nasal cavity. into the nasal cavity.
- Local treatment, the drug produces a local local treatment, the drug produces a local effect within the nasal mucosa. effect within the nasal mucosa.
- Systemic delivery, the API goes through systemic delivery, the API goes through the nasal mucosa and reaches the the nasal mucosa and reaches the general blood circulation via numerous general blood circulation via numerous capillary vessels present underneath the capillary vessels present underneath the mucosa. mucosa.
- Nasal cavity is used as a portal of entry Nasal cavity is used as a portal of entry into the blood stream into the blood stream.
Inhalation/pulmonary drug delivery system includes
- Metered dose inhalers
- Dry powder inhalers
- Inhalation nasal sprays
- Inhalation solutions & suspensions (for nebulizers)
Merits for Nasal Drug Delivery
- Avoidance of hepatic first-pass metabolism
- Rapid onset of pharmacological action
- User-friendly
- painless
- non-invasive
- needle-free administration mode
- Lower dose & hence lower side effects
- For CNS drugs, better site for rapid onset of action.
- Inhalation anesthesia, Morphine etc
Limitations
- Once administered, rapid removal of the therapeutic agent from the site of absorption is difficult
- Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailability
Pathways for nasal absorption
- Absorption through the olfactory neurons - transneuronal absorption. Olfactory epithelium isconsidered as a portal for substances to enter CN
- Absorption through the supporting cells & the surrounding capillary bed - venous drainage
- Absorption into the cerebrospinal fluid
Therapeutic class of drugs which can be delivered by nasal route
- adrenergic agonists
- Corticosteroids
- Antiviral
- Antibiotics
- vaccines
- Anti fungal
Physiological effects
- Drug metabolism in the respiratory tract & reduction of systemic effect
- Muco-ciliary transport causing increased or decreased drug residence time
- Protein binding
- Local or systemic effects of propellants, preservatives, or carriers
- Local toxic effects of the drug
Properties
- Painless
- Ease of use
- No shot needed
- Avoids first pass metabolism - improving bioavailability over oral and rectal doses
- Nose-brain pathway allows direct delivery to the cerebral spinal fluid
- Compliance not an issue - easy and fast to deliver to any patient
- Limited medications that can be delivered in this fashion
- Many medications are not adequately concentrated to achieve ideal dosing volumes
- Mucosal health impacts absorption
API properties
- Effect of particle size
- Effect of molecular size
- Effect of solution pH
- Effect of drug concentration
- Effect of drug lipophilicity
Effect of particle size
- Access to distal airways is a function of particle size
- Large particles (> 7 microns) will be lost in the gastrointestinal tract
- Intermediate particles (3 to 7 microns) reach the actual site of action
- Small particles (< 3 microns) will be lost in exhaled breaths
Effect of molecular size
- A good systemic bioavailability can be achieved for molecules with a molecular weight of up to 1000 Daltons when no absorption enhancer is used
- Higher the molecular size, lower the nasal absorption
Effect of solution pH
- Nasal absorption is pH dependent
- Absorption is lower as the pH increases beyond the dissociation constant
- Absorption is higher at a pH lower than the dissociation constant (pKa) of the molecule
Effect of drug lipophilicity
- Polar (water soluble) drugs tend to remain on the tissues of the upper airway
- Lipid soluble drugs are absorbed more rapidly than water soluble drugs
- Non-polar (lipid soluble) drugs are more likely to reach distal airways
Effect of drug concentration
- The absorption follows first-order kinetics
- Absorption depends on the initial concentration of the drug