540 - Drug Delivery Systems - Exam Iv - Nasal Drug Delivery

Front 1

What are the benefits to nasal drug delivery?

Back 1

1) Desire local effect
2) Non-invasive route to the systemic circulation
3) Possible route to access the brain

Front 2

How are drugs absorbed from the nasal cavity to the blood?

Back 2

Via transepithelial absorption - Namely paracellular and transcelluar pathways

Front 3

Which routes of administration is intra-nasal route more successful than?

Back 3

Transmucosal - buccal, pulmonary, rectal and vaginal

Front 4

What are the four conditions for application of nasal drug delivery?

Back 4

1) Rhinitis (Runny Nose)
2) Congestion
3) Systemic Drug Delivery
4) Vaccination

Front 5

What are example nasal drug delivery treatments for rhinitis?

Back 5

1) Antihistamines
2) Corticosteroids

Front 6

What are example nasal drug delivery treatments for congestion?

Back 6

1) Decongestants (vasoconstrictors)

Front 7

What are example nasal drug delivery treatments for systemic drug delivery?

Back 7

1) Hormones
2) Crisis Treatment

Front 8

What are example nasal drug delivery treatments for vaccination?

Back 8

1) FluMist (live, attenuated influenza vaccine)

Front 9

What are some benefits to intra-nasal delivery?

Back 9

1) Non-invasive
2) Lower risk of infection/disease transmission
3) Ease of self-administration/dose adjustment
4) Large SA
5) Fast onset
6) Rich vascular sucmucosa & lymphatic system
7) Avoids first pass
8) Possible direct CNS pathway

Front 10

What are some disadvantages to intra-nasal delivery?

Back 10

1) Limited to potent drugs/small volumes
2) Active mucocillary clearance
3) Enz degradation by nasal P450
4) Low permeability for hydrophilic drugs (needs large doses)
5) Low pH
6) Inter-individual variability
7) Low CNS delivery efficiencies for proteins

Front 11

What are the main factors affecting absorption of drugs from the nasal cavity?

Back 11

1) The area available for absorption
2) Contact time between the drug and absorption site
3) Metabolism in the nasal passages
4) Pathology of the absorbing tissue

Front 12

What are the four types of nasal epithelium?

Back 12

1) Squamous epithelium
2) Respiratory (ciliated pseudostratified cuboidal/columnar))
3) Transitional (non-ciliated cubodial/columnar)
4) Olfactory (cilated pseudostratified columnar)

Front 13

What is the function of the ciliated psuedostratified cubodial/columnar respiratory epithelium?

Back 13

1) Air conditioning
2) Air purficiation
3) Sense pain, temperature and touch
**Motile**

Front 14

What is the function of ciliated pseudostratified columnar olfactory epithelum?

Back 14

It mediates the sense of smell

**Non-Motile**

Front 15

What is the transgeminal nerve responsible for?

Back 15

Relaying pain, pressure and touch

Front 16

What is the first line of defense in respiratory epithelium?

Back 16

The squamous epithelium (vestibule)

Front 17

Where in the nasal passage are mobile cilia?

Back 17

Olfactory Epi (non-motile, slow clearance)
Respiratory Epi (motile, fast clearance)

Front 18

How long does it take for clearance of the bulk of mucus to move from to the nose to the nasopharynx?

Back 18

10-20 minutes --> 40% of dose is cleared rapidly in 20 minutes

Front 19

What factors effect mucocilary clearance?

Back 19

1) Cilia
2) Pericillary Fluid
3) Mucus (amount/viscosity)

Front 20

What is an example disease state indicative of compromised mucocilary clearance?

Back 20

Cystic Fibrosis

Front 21

What is the main difference between nasal and oral drug absorption?

Back 21

Nasal absorption lacks M cells/Peyer's patches

Front 22

How do drugs move from the nasal mucosa into the systemic circulation?

Back 22

Via the venous system, the drug is absorbed directly into the vein which carries it directly to the heart. This also bypasses the first pass metabolism.

Front 23

What typically damages the peripheral olfactory system?

Back 23

1) Toxins
2) Bacteria
3) Viruses
4) Drugs

Front 24

How would a nasally applied drug access the CNS?

Back 24

Via the peripheral olfactory system or transgeminal nerve

Front 25

What are four factors affecting nasal drug delivery?

Back 25

1) Disease
2) Enzymatic Activity (pseudo-1st pass effect)
3) Immunological Clearance
4) Mucous barrier

Front 26

What are examples of changes to the mucus barrier which effect nasal drug delivery?

Back 26

1) Vasoconstrictors prevent drug absorption
2) Bloody nose, congestion and mucous discharge prevent mucosal contact
3) Destruction of nasal mucosa from surgery or past cocaine use
4) Mucolytics tend to increase absorption of peptides

Front 27

What are the three general nasal drug delivery side effects?

Back 27

1) Nasal Irritation/Nose Bleeds (Physical Trauma)
2) Bad Smells/Taste (Olfactory Sys Stimulation)
3) Pain/Burning Sensation (Trigeminal Sys Stimulation)

Front 28

What are seven formulation factors of nasal drug delivery?

Back 28

1) Must be potent
2) Molecular weight, <1000 da
3) Lipohilicity (i.n. better option than p.o.)
4) pKa & pH
5) Osmolality (isotonic to slightly hypertonic)
6) Stability in processing and storage
7) Compatibility with sprayer components

Front 29

Describe nasal sprays and the disadvantage of using them

Back 29

They deposit as an aerosol of particles, droplets or particles suspended in droplets. The main problem is that they tend to deposit near the front of the nasal cavity (non-motile area) with little dose reaching the turbinates

Front 30

What is the optimal particle or droplet size range for deposit in nasal passages? What happens to particles above or significantly below this range?

Back 30

Particles or droplets in the 5 to 10 micrometers size range tend to deposit in the nasal passages. Particles larger than 10 micrometers are filtered out by the nose hairs, while particles less than 2 micrometers in size are normally not filtered out and may enter the lungs.

Front 31

What is the main problem(s) with nasal drops?

Back 31

1) They provide less reproducible dosing compared to nasal sprays
2) Awkward administration

Front 32

What is the main benefit(s) with nasal drops?

Back 32

1) Large drug dispersion throughout the length of the nasal cavity
2) Immediate drug absorption/Quick Onset
3) More drug is deposited on motile areas meaning it is cleared more quickly
4) The drug is deposited as a film of drug solution

Front 33

What are strategies for enhancing nasal permeation?

Back 33

1) Increase the area available for absorption
2) Prolong the contact time between the drug and absorption site
3) Decrease metabolism in the nasal passages
4) Understand pathology of the absorbing tissue