Nasal Drug Delivery

Question 1

Conditions for which drugs need to be administered through the nasal cavity

Answer 1

• Cold/Sinusitis - decongestants
• Allergic rhinitis - antihistamines
• Nasal infections - antibiotics, antiseptics
• Epistaxis - bismuth iodoform paraffin paste

Question 2

5 regions of the nose

Answer 2

A) Vestibule

B) Atrium

C) Respiratory region

D) Olfactory region

E) Nasopharynx

Question 3

What are Turbinates in the nose

Answer 3

Curled spongy bones that protrude in the nasal passages

• Create air turbulences
• Role in air humidification, heating, filtration and in olfaction
• Increase surface for absorption

Question 4

4 cell types in respiratory epithelium

Answer 4

Ciliated cells

Non-ciliated cells

Goblet cells

Basal cells

Covered by mucus

Similar to tracheal/bronchial epithelium

Question 5

Describe Mucus

Answer 5

• Composed of: water (90-95%), salts, glycoproteins, enzymes, immunoglobulins, lysozyme (kill microorganisms)
• pH: 5.5-6.5
• Biphasic = more viscous gel phase rests above a less viscous sol-phase
• Protects epithelium from dehydration, microorganisms + inhaled particles
• Particles trapped in mucus move towards nasopharynx by cilia + swallowed (mucociliary clearance) - turnover = 15-20 min

Question 6

Characteristics of vestibule

Answer 6

Stratified squamous, keratinized epithelium

<1 cm² SA

Low vascularisation

Poor Permeability

Question 7

Characteristics of atrium

Answer 7

Stratified, squamous epithelium

5-10 cm² SA

Low vascularisation

Poor permeability

Question 8

Characteristics of respiratory region

Answer 8

Pseudostratified columnar epithelium

130 cm² SA

Very high vascularisation

Good permeability

Question 9

Characteristics of olfactory region

Answer 9

Pseudostratified columnar epithelium + olfactory receptors

15 cm² SA

High vascularisation

Good permeability (direct access to CNS)

Question 10

What nasal area is best for drug delivery

Answer 10

Respiratory region

Question 11

Where are drugs mainly absorbed from in the nasal cavity?

Answer 11

Respiratory region

• large SA
• High vascularisation
• Prolonged contact time
• Drug diffuses into systemic circulation from respiratory region
• Rapid absorption
• High inter-patient variability

Question 12

Mechanisms for absorption into the respiratory region of the nose

Answer 12

Passive diffusion (transcellular, paracellular)

Transcytosis

Receptor-mediated transport

• can be envisaged for non polar and polar (including peptides) drugs

Question 13

Drugs administered to the nasal cavity for systemic action

Answer 13

• Pain - fentanyl, butorphanol
• Migraine - sumatriptan, zolmitriptan
• Hormone replacement – estradiol
• Smoking cessation – nicotine
• Labour induction, lactation simulation – oxytocin
• Osteoporosis – calcitonin
• Prostate cancer – buserelin (LHRH analogue)
• Endometriosis – buserelin, nafarelin (LHRH analogues)
• Diabetes insipidus – desmopressin (vasopressin analogue)
• Flu prevention – live attenuated influenza vaccine

Question 14

Advantages of nasal delivery for systemic action

Answer 14

• Easy access
• Non-invasive/painless
• Avoids GIT (acidic pH, enzymes)
• Rapid absorption, rapid onset of action
• Easy formulation
• Avoids FPM

Question 15

Disadvantages of nasal drug delivery

Answer 15

• Small cavity - 100-150 microlitre formulation can be delivered
• Mucociliary clearance - drug cleared in 15-20 min
• Mucus can be a barrier to absorption
• High levels of cytochrome P450 + proteases
• Drug molecular weight (low absorption if MW > 1kDa
• Nasal irritations
• Taste/smell issues

Question 16

Nasal drug delivery systems

Answer 16

Creams, Ointments

Nasal drops

Nasal sprays

Question 17

Formulation design of nasal drug delivery

Answer 17

• Critical as very sensitive area
• Liquid formulations must match nasal secretions
  
  • Aqueous
  • Isontonic
  • pH close to physiological values of 3 - 10
  • Sterility not required
• Must not interfere with ciliary interference
  
  • Issues with viscosity enhancers + preservatives
• Common ingredients = antioxidants + co-solvents

Question 18

What is nasal irrigation

Answer 18

Rinsing nostrils with saline solution

• To flush out allergens, debris + microorganisms
• Fluidises mucus
• Relieve symptoms of rhinitis/sinusitis
• Must used sterile/ fr4eshly boiled + cooled water

Question 19

Nasal delivery of peptides

Answer 19

To avoid frequent injections

Mostly under development

All short peptides

Bioavailabiltiy is low (1.5%)

Question 20

Why is there low bioavailability when delivering peptides to the nose?

Answer 20

• Low absorption due to high molecular weight
• Enzymatic degradation in the nose
• High doses must be delivered

Question 21

Nasal vaccines

Answer 21

Better than injections

• painless
• patient acceptance

Influenza nasal vaccines

• live attenuated
• cause disease in some [atients
• only for healthy 2-49 individuals
• must be stored frozen
• cost 7x more than IM vaccines

Question 22

Nasal sprays

Answer 22

Aerosols of droplets/solid particles

• particles must be >50 micrometres/ they enter lung
• deposition by inertial impaction
• Easy to administer
• Penetrate deeper into nasal cavity
• Liquid sprays preferred (less irritation, easier formulation but stability issues)

Question 23

Nasal drops

Answer 23

Solution/suspension delivered using dropper bottle

• Good spread in the nasal cavity
• Dose delivered is not accurate
• Correct application is quite complex