Pulmonary Drug Delivery I

Question 1

Why delivery drugs via the respiratory route?

Answer 1

1. local affect - rapid onset of activity
2. Smaller doses - economical and lower s.e
3. HIGH first pass metabolism - bioavailability uses
4. High lung surface area and good blood supply makes provides potential for systemic delivery

Question 2

Give an example of bronchodilator?

Answer 2

Salbutamol

Question 3

Funamentals of Pulmonary drug delivery?

Answer 3

1) drug physiochemical properties

2) Formulation

3) Patient

4) Delivery systems

Question 4

dp

Answer 4

physical diameter

Question 5

p

Answer 5

particle density

Question 6

p0

Answer 6

unit density

Question 7

Drugs are usually delivered to the lungs as _______

Answer 7

• Solid particles suspended in the air
• Liquid particles suspended in the air

Question 8

Gases are also sometimes administered via the pulmonary route, e.g.

Answer 8

ocygen

anaesthetics

Question 9

What do we call the diameter of a sphere of which settles through air with a velocity equal to that of the particle in question?

Answer 9

Aerodynamic diameter (da)

Question 10

Label the following:

Answer 10

• nasal cavity
• Nasopharynx
• Epiglottis
• tongue
• oesophagus
• largynx
• trachea
• mainstem bronchus
• lobar bronchus
• segmented bronchus
• bronchiole
• alveolus
• Pleural effusion

Question 11

inertial impaction

Answer 11

inertial impaction tends to occur in upper airways when velocity and mass of particles cause them to impact the airway surface

Question 12

Impaction depends on:

Answer 12

• particle momentum (size dependent)
• position of particle in airstream of the parent branch
• angle of bifurcation

Question 13

sedimentation

Answer 13

particles suspended in a GAS are subject to the vertical gravitational force

• sedimentation is the dominant mechanism for particles depositing in the lower / peripheral airways

Question 14

Diffusion

Answer 14

dominant mechanism for particles < 0.5um

smaller particles, more they DEPOSIT via diffustio in peripheral lung and alveolar space

Question 15

Minor mechanisms of deposition:

Answer 15

interception for elongated particles

charge reflection for charged particles

Question 16

label the trachea down to alveolus

Answer 16

• trachea
• mainstem bronchus
• lobar bronchus
• segmental bronchus
• bronchiole
• alveolar duct
• alveolus

Question 17

Drug Delivery Devices
3 categories

Answer 17

1. Pressurised metered-dose inhalers (pMDIs)
2. Dry powder inhalers (DPIs)
3. Nebulisers
4. Electronic cigarettes

Question 18

Pressurised metered-dose inhalers (pMDIs)

Answer 18

Drug is dispersed in the liquid propellant – may be in solution or a suspension

Dose (set volume) released on actuation of a metering valve

Question 19

pMDI mechanism of action

Answer 19

Canister: typically aluminium

Propellant: hydrofluoroalkanes

Metering valve: controls the volume delivered

Question 20

study graph - phase diagram

Answer 20

solid
liquid
gas

against pressure and temperature

Question 21

Propellants used are ________ gases

Answer 21

liquified

Question 22

Filling of pMDI canisters

Answer 22

1) Cold filling

2) Pressure filling

Question 23

Cold filling

Answer 23

Drug + excipients + propellant chilled to 60 °C and added to canister

Further (chilled) propellant added and canister sealed (with the valve)

QC: leak tested – placed in water bath and then weighed

Question 24

Pressure filling

Answer 24

Drug + excipients + propellant added to canister under pressure (through the valve)

Further propellant (under pressure) added

QC: leak tested – placed in water bath and then weighed

Question 25

Formulation of pMDIs

Answer 25

pMDIs originally contained chlorofluorocarbons (CFCs) but discovered in 1980s that these damaged the ozone layer
CFCs removed from pMDIs during the late 1990s/ early 2000s and replaced with hydrofluoroalkanes (HFAs)

HFAs still greenhouse gases and will need to be phased out

Question 26

pMDIs - what can druyg be dispersed in?

Answer 26

in the propellant as a solution ( two phase system0 or suspension (three-phase system)

Question 27

HFA-134a and HFA-227 exhibit ___ relative permittivity values so are not good solvents for many drugs (or excipients)

Answer 27

low

Question 28

Surfactants:

Answer 28

Lecithin
Oleic acid
Sorbitan trioleate

Previously used at 0.1% to 2.0% w/w in CFC-based inhalers
Solubility <0.02% w/w in HFAs hence requires cosolvent (ethanol)

Question 29

When beclometasone dissolved in the propellant this can lead to

Answer 29

very SMALL particles (MORE POTENT)

Some formulations include a less volatile solvent, e.g. Clenil Modulite:

Question 30

pMDIs and sustainability

Answer 30

pMDIs are bulky dosage forms that use plastics and aluminium
Both recyclable but no national recycling schemes exist

Question 31

Ventolin vs Salamol

Answer 31

Ventolin brand salbutamol inhaler is not included in the All Wales Adult Asthma Management and Prescribing Guideline

Question 32

advantages of pMDIs

Answer 32

• portable
• low cost
• drug protected from enviroment in canister
• multiple doses in one device
• reproducible dose
• efficiemt at drug delivery (oral route)
• disposable

Question 33

disadvantages of pMDIs

Answer 33

• incorrect use by pateints
• greenhouse gases
• disposable - why?