Nasal Flashcards
Nasal delivery
Local effect, fast acting, more effective than other transmucosal routes
Non-invasive route to systemic circulation
Possible route directly to the brain
Application of nasal drug delivery
Rhinitis
Congestion
Systemic delivery
Vaccination
Intranasal advantages
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
Intranasal disadvantages
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
Factors affecting absorption of drugs from the nasal cavity
Area of absorption
Contact time between drug and absorption site
Metabolism in nasal passages
Pathology/disease of absorbing tissue
Nasal epithelium functions
Warmth, humidity, filter
Types of nasal epithelium
Squamous epithelium
Respiratory
Transitional
Olfactory
Respiratory epithelium
80-90% of nasal cavity SA
Function:
—air conditioning
—air purification (1-10mm/min)=rapid mucocilliary CL
—sense pain, temperature, touch
Olfactory epithelium
<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
Mucocilliary clearance
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
Transport mechanisms across the nasal epithelium
Transcellular
Paracellular
Transcytosic (through vessel)
Absorption into lymphatic circulation via M-cells of Peyer Patches facilitates immune system functions
After nasal absorption
Absorption into venous circulation of nasal passages
Nasal vaccinations
NALT—located in the middle turbinate
—all components needed for antigen specific immune responses
—target site for nasal vaccines
Flumist
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
Olfactory deficits are common in
Alzheimer’s and Parkinson’s
Drugs perceived as noxious/bad smelling
Present compliance issues
Other factors affecting nasal drug delivery
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
Nasal drug delivery side effects
Nasal irritation/nose bleeds
Experience bad smells/tastes
Pain/burning sensation
Nasal sprays
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
Optinose
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
Impel neuropharma
Device designed to deliver spray to olfactory area
Nasal drops
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
When are nasal drops preferred
For rapidly absorbed drugs because drops are more rapidly cleared in the second phase of clearance than sprays
Strategies for enhancing area of absorption
Erode mucosal surface using penetration enhancers
Osmotic strategies
Strategies for prolonging contact time
Modify deposition site
Increase viscosity
Use bioadhesives
Reduce Mucocilliary clearance rate by affecting ciliary movement
Strategies to decrease metabolism in nasal passages
Use protease inhibitors
Strategies to enhance nasal permeation
Increase area
Prolong contact time
Decrease metabolism
Understand the pathology
