Nasal drug delivery

Question 1

Why deliver drugs to the nasal cavity?

Answer 1

• local drug delivery
  allergic rhinitis, congestion, infection
• systemic absorption
  diabetes insipidius, migraine, prostate cancer, osteoporosis

nasal drug delivery results in a faster systemic absorption than oral drug delivery

to deliver peptides

Question 2

Advantages of nasal drug delivery

Answer 2

• high vascularisation due to blood supply close to surface of mucosa
• accessbility
• ease of admin
• reduced first pass metabolism
• low metabolic activity compared to GI tract
• large surface area

Question 3

Disadvantages of nasal drug delivery

Answer 3

• low pH may lead to irritancy- SIDE EFFECTS
• limited dose
• patients may find it difficult to administer- REPRODUCIBILITY
• reduced absorption due to mucus- more than in lungs
• LOW residence time

Question 4

What is the nasal cavity?

Answer 4

the upper airways

Question 5

Function of the nose

Answer 5

• olfaction
• air conditioning due to high vascularisation which humidifies the air

does not recieve drugs for systemic absorption

Question 6

Structure of the nose

Answer 6

• length of nasal cavity is 12-14cm
• volume holds 10-14cm3
• divided by the nasal septum
• vestibule 1.5cm long vibrasse
• ends in the internal ostium (nasal valve) which is the narrowest part of the airway

Question 7

Fate of particles delivered to the nose

Answer 7

> 10 micrometres is filtered by the vibrasse
5-10 micrometres deposits in the nasal passages and is subject to mucociliary clearance
<2 micrometres passes through to the lungs

Question 8

Structure of the respiratory epithelium

Answer 8

ciliated columnar cells
goblet cells
non-ciliated columnar cells
basal cells

Question 9

Mucus

Answer 9

• from serous glands and goblet cells
• form viscous gels due to high molecular weight mucins and ability to form disulphide bridges

function: air conditioning and to trap things

Question 10

Composition of mucus

Answer 10

water 90-95%
mucins 0.5-5% (responsible for gel like structure)
lipids 2-3%
salts 1-2%

Question 11

Mucociliary clearance

Answer 11

cilia have hooks which beat in a coordinated manner

continuously move foreign material to the back of the throat

low return stroke so continuously push waft forward

Question 12

Types of preparations used in nasal drug formulations?

Answer 12

for topical therapy and systemic absorption in prescription medicines

otc

non- drug preparations

Question 13

devices used to administer nasal drug formulations

Answer 13

drops- easiest- must rest head on one side for 30 seconds

sprays

powders- less popular but may be used to administer peptides that are usually unstable

gels
ointments- difficult to get into nasal cavity

Question 14

Formulation factors

Answer 14

drug concentration

dose

formulation pH- affects solubility

formulation osmolarity

physical form

volume

Question 15

peptide delivery

Answer 15

alternative to oral dosing for peptide hormones

inverse relationship between absorption and size (max 14 amino acids)

peptidase enzymes limit bioavailability

Question 16

Name some intranasal peptides < 10 amino acids

Answer 16

• desmopressin spray and drops

- buserelinspray

Question 17

Name some intranasal peptides > 10 amino acids

Answer 17

• salmon calcitonin nasal spray

1% bioavailability

32 amino acids
used for osteoporosis

• insulin

Question 18

peptide and protein degrading enzymes

Answer 18

carboxypeptidase
aminopeptidase
endopeptidase
protease

Question 19

What promotes nasal peptide and protein absorption by increasing permability

Answer 19

surfactants and bile salts

Question 20

what promotes peptide absorption by making tight junctions open up a bit

Answer 20

chelating agents

fatty acids

Question 21

what other excipients promote nasal peptide and protein absorption?

Answer 21

• enzyme inhibitors- less presystemic loss to metabolism

- bioadhesive delivery systems –> longer retention