Lecture 17 Nasal Drug Delivery Flashcards
(37 cards)
Describe the anatomy of the respiratory region involved in nasal drug delivery. What are the characteristics of the three scroll-shaped bony elements in the nasal cavity? How do they contribute to the nasal cavity’s surface area and air flow?
The anatomy of the respiratory region for nasal drug delivery includes three thin scroll-shaped bony elements known as nasal conchae or turbinates. These structures create air passages in the nasal cavity, increasing its surface area significantly compared to its volume, facilitating efficient airflow.
What are the different morphological features present in the respiratory region relevant to nasal drug delivery? Explain the roles of ciliated cells, non-ciliated cells, goblet cells, gel mucus layer, sol layer, basal cells, and basement membrane in the nasal cavity.
The respiratory region involved in nasal drug delivery contains various features like ciliated cells, non-ciliated cells, goblet cells, gel mucus layer, sol layer, basal cells, and basement membrane. These components work together to maintain the nasal cavity’s function, including mucus secretion, cell protection, and structural support.
Describe the basic functions of the nose and nasal secretions.
The nose functions in heating, humidification, olfaction, resonance, and defense through filtration, mucociliary clearance, and antimicrobial actions. Nasal secretions, mainly mucus, protect the mucosa, aid in heat transfer, regulate cilia beat, and facilitate ion transport.
How does mucociliary clearance work in the nasal passages?
Mucociliary clearance involves a mucus blanket with two layers - a low viscosity sol layer and a highly viscous gel layer. Particles adhere to the mucus, get transported by cilia towards the nasopharynx, and are eventually discharged into the gastrointestinal tract to prevent respiratory infections.
Define the composition and production of nasal secretions.
Nasal secretions primarily consist of mucus produced by submucosal glands and goblet cells. Mucus covers the mucosa, providing physical and enzymatic protection, facilitating heat transfer, regulating cilia beat, and aiding in ion transport. Approximately 1.5-2 liters of mucus are produced daily.
What are the key components of the mucus blanket in mucociliary clearance?
The mucus blanket in mucociliary clearance consists of two layers - a lower sol layer with low viscosity that bathes the cilia, and an upper gel layer with high viscosity. Particles adhere to the mucus lining, are transported by cilia towards the nasopharynx, and are expelled into the gastrointestinal tract.
Describe the importance of maintaining proper mucociliary clearance in the respiratory system.
Maintaining effective mucociliary clearance is crucial to prevent lower respiratory tract infections. Any impairment in the mucus or cilia function can hinder the clearance of particles, such as dust, bacteria, and viruses, leading to potential respiratory issues.
Describe the rationale for intranasal drug delivery and its advantages over intravenous injection.
Intranasal drug delivery is favored due to the thin, porous nasal epithelium with high permeability, large surface area, direct systemic circulation transport, potential nose-to-brain delivery, lower enzymatic activity than the gastrointestinal tract, self-medication feasibility, enhanced patient compliance, and reduced risk of over-dosage.
What are the limitations of intranasal drug delivery despite its advantages?
Limitations include the limited volume of the nasal cavity, restricted absorption of large hydrophilic molecules, presence of an enzymatic barrier, mucociliary clearance with a half-life of approximately 21 minutes, irregular deposition, and potential mucosa sensitivity.
How can an optimal nasal drug delivery system be defined in terms of drug candidate characteristics?
An optimal system requires a drug candidate with suitable aqueous solubility and absorption properties, minimal nasal irritability (lack of toxic metabolites or noxious odors), rapid onset of action, low dosage (<25 mg), stability, and compatibility with the drug delivery device.
Explain the potential for nose-to-brain delivery in intranasal drug administration.
Nose-to-brain delivery is feasible due to nerves penetrating the upper olfactory region of the nasal cavity, allowing drugs to bypass the blood-brain barrier and directly target the brain. This route offers a promising approach for treating neurological disorders.
What are the key advantages of using intranasal drug delivery as an alternative to other routes of administration?
Intranasal delivery offers advantages such as rapid onset of action, direct systemic circulation transport, potential nose-to-brain delivery, lower enzymatic activity compared to the gastrointestinal tract, self-medication feasibility, enhanced patient compliance, and reduced risk of over-dosage.
Describe the products that use the intranasal route for systemic delivery. Include examples of hormones, analgesics, and vaccines administered through this route.
Products using the intranasal route for systemic delivery include hypothalamic hormones like buserelin and nafarelin, other hormones like desmopressin, antimigraine medications like sumatriptan, opioid analgesics like fentanyl, and vaccines like Fluenz (FluMist). These products are administered as nasal sprays or suspensions for various medical indications.
How is Fluenz (FluMist) administered and what are its key characteristics?
Fluenz (FluMist) is administered as a divided dose in both nostrils. It is a live, attenuated influenza vaccine containing strains of influenza A and B. The vaccine may contain residues of egg protein and gentamicin. It is a colorless to pale yellow suspension with small white particles. The dosage is 0.2 ml, with 0.1 ml administered per nostril.
Define the indication and dosage of Fluenz (FluMist) for prophylaxis of influenza in individuals.
Fluenz (FluMist) is indicated for the prophylaxis of influenza in individuals aged 24 months to less than 18 years, excluding contraindications. The dosage is 0.2 ml, administered as 0.1 ml per nostril using a single-use glass applicator with various components.
Describe the components of the single-use glass applicator used for administering Fluenz (FluMist) intranasally.
The single-use glass applicator for Fluenz (FluMist) includes a nozzle, nozzle tip-protector cap, plunger rod, plunger-stopper, and a dose-divider clip. These components are essential for the accurate and safe administration of the vaccine in both nostrils.
Do patients need to actively inhale or sniff during the administration of Fluenz (FluMist)?
No, patients do not need to actively inhale or sniff during the administration of Fluenz (FluMist). They can breathe normally while the vaccine is being administered, making the process more comfortable and convenient for the individual receiving the intranasal vaccine.
Describe the role of the mucus layer in drug absorption and how it impacts the passage of different types of particles.
The mucus layer plays a crucial role in drug absorption by serving as a barrier. Low molecular weight, non-polar particles can easily pass through, while larger or charged particles face difficulty. Factors like structural and environmental changes, temperature, pH, and the presence of mucin influence the movement of particles.
How do different mechanisms like Paracellular Pathway, Transcellular Pathway, Transcytosis, and Receptor-mediated pathways contribute to drug absorption through the nasal mucosa?
Various mechanisms such as Paracellular Pathway, Transcellular Pathway, Transcytosis, and Receptor-mediated pathways play a role in drug absorption through the nasal mucosa. The pathway chosen depends on the molecular weight and lipophilicity of the drug substance.
Define the impact of physiological factors like mucociliary clearance (MCC) on drug absorption through the nasal mucosa.
Physiological factors like mucociliary clearance (MCC) influence drug absorption through the nasal mucosa. MCC affects the diffusion path, leading to a rapid rise in peak plasma concentrations but also limits the available time for absorption due to rapid clearance from the mucosa.
Describe how stability, enzymatic degradation, nasal blood flow, and pathological conditions can affect drug absorption through the nasal mucosa.
Factors like stability, enzymatic degradation by enzymes like cytochrome P450, carboxylesterases, and glutathione S-transferases, nasal blood flow influenced by vasodilators/vasoconstrictors, and pathological conditions such as infection or nasal obstruction can impact drug absorption through the nasal mucosa.
Explain the significance of molecular weight and lipophilicity of drug substances in determining the absorption pathway through the nasal mucosa.
The molecular weight and lipophilicity of drug substances are crucial in determining the absorption pathway through the nasal mucosa. These factors dictate whether the drug will follow pathways like Paracellular, Transcellular, Transcytosis, or Receptor-mediated for absorption.
Describe the physicochemical factors that influence nasal drug absorption.
Physicochemical factors affecting nasal drug absorption include molecular size (above 1000 Da decreases absorption), pH (ideal range 4.5-6.5 for mucosa health and drug availability), lipophilicity, osmolarity, viscosity, density, and concentration/dose/volume.
How does pH impact nasal drug absorption and why is a specific range preferred?
pH affects nasal drug absorption by influencing mucosa irritation, MCC & lysozyme activity, and drug ionization for absorption. A pH range of 4.5-6.5 is preferred to maintain mucosa health and enhance drug availability.
