Nasal

Question 1

Nasal delivery

Answer 1

Local effect, fast acting, more effective than other transmucosal routes
Non-invasive route to systemic circulation
Possible route directly to the brain

Question 2

Application of nasal drug delivery

Answer 2

Rhinitis
Congestion
Systemic delivery
Vaccination

Question 3

Intranasal advantages

Answer 3

Noninvasive/reduced infection risk/low risk disease transmission
Easy self-admin/dose adjustment
Large SA for absorption
Rapid absorption/fast onset
Rich, vascular submucosa and lymphatic system
Avoid hepatic first-pass elimination
Possible direct passage to CNS bypassing BBB

Question 4

Intranasal disadvantages

Answer 4

Limited to potent drugs/small V
Mucocilliary clearance
Enzymatic degradation by CYPs/peptidases/proteases
Low permeability for hydrophilic drugs
Low pH of nasal epithelium (5.5-6.5)
Interindividual variability
Low CNS delivery efficiencies for proteins thus far

Question 5

Factors affecting absorption of drugs from the nasal cavity

Answer 5

Area of absorption
Contact time between drug and absorption site
Metabolism in nasal passages
Pathology/disease of absorbing tissue

Question 6

Nasal epithelium functions

Answer 6

Warmth, humidity, filter

Question 7

Types of nasal epithelium

Answer 7

Squamous epithelium
Respiratory
Transitional
Olfactory

Question 8

Respiratory epithelium

Answer 8

80-90% of nasal cavity SA
Function:
—air conditioning
—air purification (1-10mm/min)=rapid mucocilliary CL
—sense pain, temperature, touch

Question 9

Olfactory epithelium

Answer 9

<10% nasal cavity SA
Function: sense of smell
Particularly vulnerable to damage
May allow direct transport of certain drugs to nasal passages in the brain

Question 10

Mucocilliary clearance

Answer 10

Part of body’s defense mechanisms
Mucosal cilia beat in a coordinated manner to propel mucus towards the nasopharynx
~40% of administered dose is cleared rapidly in 20 min
Compromised clearance = cystic fibrosis causes mucus dehydration —>poor clearance

Question 11

Transport mechanisms across the nasal epithelium

Answer 11

Transcellular
Paracellular
Transcytosic (through vessel)
Absorption into lymphatic circulation via M-cells of Peyer Patches facilitates immune system functions

Question 12

After nasal absorption

Answer 12

Absorption into venous circulation of nasal passages

Question 13

Nasal vaccinations

Answer 13

NALT—located in the middle turbinate
—all components needed for antigen specific immune responses
—target site for nasal vaccines

Question 14

Flumist

Answer 14

Approved flu vaccine
M cells transport antigen across epithelium to dendritic cells—>stimulate T&B cells—>stimulated cells migrate to lymph nodes then to blood all over body, particularly to nasal passage and intestinal mucosa—>IgA secreted into nasal and intestinal mucus—>protection

Question 15

Olfactory deficits are common in

Answer 15

Alzheimer’s and Parkinson’s

Question 16

Drugs perceived as noxious/bad smelling

Answer 16

Present compliance issues

Question 17

Other factors affecting nasal drug delivery

Answer 17

Disease (common cold, hay fever)
Enzymatic activity
Immunological clearance (IgA)
Mucus barrier—mucolytics increase absorption of peptides
Vasoconstrictors—prevent absorption
Bloody nose, nasal congestion, and mucus discharge—prevent absorption
Mucosa destruction—prevent absorption

Question 18

Nasal drug delivery side effects

Answer 18

Nasal irritation/nose bleeds
Experience bad smells/tastes
Pain/burning sensation

Question 19

Nasal sprays

Answer 19

Deposit at the front of the nasal cavity with little dose reaching the turbinates
Size: 5-10 um
Bigger particles are filtered by nose hairs in the nostril
Smaller particles less than 2 um enter the lungs

Question 20

Optinose

Answer 20

Device results in widespread distribution in the nasal passage, patient exhales through device to drive spray into the nasal passage. Soft palate closes with exhalation

Question 21

Impel neuropharma

Answer 21

Device designed to deliver spray to olfactory area

Question 22

Nasal drops

Answer 22

Simplest and most convenient formulation
Less reproducible dosing compared to nasal sprays
Disperse a drug solution throughout the length of the nasal cavity from the vestibule to the nasopharynx
—large area for absorption
—more drug is cleared/swallowed
More dependent on method of application

Question 23

When are nasal drops preferred

Answer 23

For rapidly absorbed drugs because drops are more rapidly cleared in the second phase of clearance than sprays

Question 24

Strategies for enhancing area of absorption

Answer 24

Erode mucosal surface using penetration enhancers
Osmotic strategies

Question 25

Strategies for prolonging contact time

Answer 25

Modify deposition site
Increase viscosity
Use bioadhesives
Reduce Mucocilliary clearance rate by affecting ciliary movement

Question 26

Strategies to decrease metabolism in nasal passages

Answer 26

Use protease inhibitors

Question 27

Strategies to enhance nasal permeation

Answer 27

Increase area
Prolong contact time
Decrease metabolism
Understand the pathology