Nasal Drug delivery

Question 1

Describe the anatomy nasal cavity?

Answer 1

1. Nasal cavity is lined with mucosal membrane
2. Microvilli attach to the surface of the blanket
3. Columnar cells covered by cilia and microvilli
4. Basal cells
5. Goblet cells: packed with mucus
6. Non columnar cells: covered with microvilli of similar length

Question 2

Explain the function of the nasal cavity?

Answer 2

1. Secretes more moisture to humidifies airs to bring the temperature in the environment to normal temperature in the body
2. Man’s air conditioner

Question 3

Describe how the particulates are removed by the nose?

Answer 3

1. Vibrisae in nostrils filter particulates (10 micrometers)
2. Process of Mucocillary cleared as mucus is produced continuously (5-10 micrometers)
3. Particles less than 2 micrometers are inhaled in by the lungs

Question 4

Describe how mucocillary clearance works?

Answer 4

1. Dust and organisms are trapped by the viscoelastic mucus blanket that lines the nasal passage
2. The cilia wafts the mucus in continuous fashion towards the nasal pharynx where mucus is swallowed or spat out as phlegm
3. Digested and destroyed by stomach acid

Question 5

Describe what the nasal mucus purpose is?

Answer 5

1. Trap dust and organisms in mucus which is cleared via mucocillary clearance
2. Holding of water permits humidification of inspired air and aid heat transfer
3. Presents a diffusion barrier

Question 6

What are the medicinal agents that are applied in the nasal route?

Answer 6

1. Drugs for the alleviation of nasal symptoms such as nasal allergies, congestion and infection
2. Provides an alternative to intravenous and oral route (and peptides/proteins) if the drug is destroyed by the stomach

Question 7

What other part of the body does the nasal route have access to when medicinal products used?

Answer 7

1. Central Nervous System
2. 1 to 2% bioavailability when nasal route used
3. Direct connection between CNS and atmosphere

Question 8

Give an example of a drug that’s given intranasally for the purpose of analgesic action, CNS stimulant and cardiovascular drug?

Answer 8

1. Analgesic: morphine
2. CNS: cocaine and nicotine
3. Cardiovascular: propranolol

Question 9

What are the advantages of nasal route administration?

Answer 9

1. There’s a large surface area that’s highly vascularised with many blood vessels ensures rapid absorption and onset of action
2. Ease of administration
3. Can bypass the blood brain barrier to achieve CNS effects
4. Low metabolic activity

Question 10

What are the disadvantages of nasal route administration?

Answer 10

1. Mucocillary clearance
2. Mucous barrier: if it doesn’t have time to pass the barrier, it’ll get washed away in the body
3. Adverse effects: mucous lining is very sensitive
4. Diseases can affect the absorption of the drug: runny nose
5. Limited to potent molecules
6. Metabolic activity

Question 11

Describe what the formulation factors will depend on when forming a drug for nasal route administration?

Answer 11

1. Molecular weight of the dosage form: larger the more difficult to pass through
2. Concentration of the dosage form
3. pH
4. Tonicity: effect of diffusion it has
5. Particle size
6. Viscosity: water soluble polymers like methyl cellulose decrease mucous cillary rate due to high visosity

Question 12

Describe the molecular weight in terms of formulation for nasal route administration?

Answer 12

1. The lower the molecular weight (less than 1000 Da), the more permeable it is to be absorbed (high bioavailability)
2. The higher the molecular weight (more than 6000 Da), most likely it cannot cross membrane without damaging mucosal membrane (low bioavailability)
3. Drug absorption is more in nasal than oral

Question 13

Describe the effect of pH in terms of formulation for nasal route administration?

Answer 13

1. The mucus membrane is slightly acidic (5.5 to 6.5)
2. The pH partitioning hypothesis is correct that the less ionised the drug, the more permeable it is through the membrane
3. Cationic drugs (+) can bind to negatively charged mucous glycoproteins which may reduce absorption
4. pH may change the absorption of peptides

Question 14

Describe the effect of concentration in terms of formulation for nasal route administration?

Answer 14

1. The rate of diffusion through the nasal membrane is via paracellular (cell junction) or transcellular (through epithelial cell)
2. The higher the concentration, the more permeable it is
3. High concentrations can lead to adverse side effects as the mucosal lining is very sensitive
4. In a solution, the highest concentration is sought after in conjunction to the correct amount of liquid

Question 15

Describe the effect of particle size in terms of formulation for nasal route administration?

Answer 15

1. The larger the particle size, the more likely it’ll end up in the lung
2. Nanoparticles of cocaine have been found in the lungs

Question 16

Describe what nasal drops are?

Answer 16

Disperses a solution from the atrium to the nasalpharynx to offer immediate area for absorption

Question 17

Describe what nasal sprays are?

Answer 17

Deposit at the nasal cavity with little of the dose reaching turbulence

Question 18

Explain how nasal drops and sprays may be better than one another in different areas?

Answer 18

1. Nasal drops are more rapidly absorbed in the nasal cavity but are 40% more rapidly cleared by mucosal clearance
2. Nasal sprays are more slowly spread through the epithelium and will need longer contact time

Question 19

What is the correct procedure to administer a nasal drop?

Answer 19

1. Laying on your back
2. Dropping it into nose
3. Tipping head back
4. Standing up

Question 20

What are the strategies for improving nasal formulation?

Answer 20

1. Enhance nasal absorption
2. Enhance drug residency time
3. Change functional groups and drug structure to modify physicochemical properties

Question 21

What are the mechanisms in the drugs that alter the mucosa to promote absorption?

Answer 21

1. Alteration of mucus layer, cationic and anionic surfactants can decrease viscoelasticity
2. Alteration of tight junctions, substances that sequester extracellular calcium ions will open up tight junction gaps
3. Reversed micelle formation: hydrophilic inside and hydrophobic outside, will cross barrier more easily
4. Extraction by co-micellisation
5. Erosion of mucosal surface

Question 22

Describe what the use of cyclodextrins are?

Answer 22

1. Used to solubilise drugs so that they are more efficient when it comes to absorption
2. Increases the concentration of drug in aqueous solution

Question 23

Describe the use and give examples of dry powder adhesives in drug for the nasal cavity?

Answer 23

1. Examples: Microcrystalline, cellulose and starch
2. Drugs absorb water and form viscous gels in the nasal mucosa
3. Remain in the cavity for 6 hours