Respiratory medicines drug delivery

Question 1

What are two examples of inhalers that have a ICS + LABA + LAMA formulation?

Answer 1

Trimbow (pMDI) and Trelegy Ellipta (accuhaler)

Question 2

What are the benefits of using combination therapy? (triple therapy)

Answer 2

-Increased patient compliance (a patient is more likely to use one inhaler than three separate ones).
-Positive drug interactions, enhances bronchodilatory effects

Question 3

When somebody with COPD presents with a chest infection what is usually prescribed?

Answer 3

Broad spectrum antibiotic (Amoxicillin 500mg tabs TDS 5 days)
Oral steroid (Prednisolone 5mg tabs 8 tablets a day for 5 days)

Question 4

What is the optimum binding of API to a carrier (for example lactose)?

Answer 4

Compromised binding to the lactose
-Weak interactions means air flow is reduced but dispersal of API is good (aerosolisation)
-Strong interactions means air flow is good but aerosolization is poor (API particles can’t disperse when bound tightly to the lactose carrier particles)

Question 5

What does API stand for?

Answer 5

Active pharmaceutical ingredient

Question 6

What are four examples of Long-acting muscarinic antagonist drugs?

Answer 6

Tiotropium
Glycopyrronium
Aclidinium
Umeclidinium

Question 7

Why is particle size crucial for optimum drug delivery?

Answer 7

-If the particles are too small (0.5 microns to 1 microns) deposition will most likely deposit further than intended in the alveoli and it is likely they will reach systemic circulation.
-If the particles are too larger (greater than 5 microns) deposition will most likely occur in the upper respiratory tract due to inertial impaction.

Question 8

What are the side effects associated with deposition in the upper respiratory tract and the alveoli?

Answer 8

If API particles are deposited in the upper respiratory tract can cause a dry/ tickly cough as particles irritate lining of the respiratory epithelial cells.
If API particles are deposited in the alveolar region as absorbed systemically there is a chance of tremors, headaches.

Question 9

A patient is currently prescribed a Salbutamol inhaler (MDI) and a Clenil inhaler (MDI) and is found he is having to use his salbutamol inhaler every day and he is also experiencing a dry cough present particularly after using his inhaler, what changed would you make a why?

Answer 9

-Introduce a spacer, poor inhaler technique is probably resulting in high particle deposition in the back of the throat/ upper airways.
-A spacer will reduce the need for co-ordination between actuation and inhalation in addition to reducing particle size as larger particles will deposit in the spacer meaning less deposition in the upper airways.
-Probably getting a sub-optimal dose at the moment, that’s why he is having to use it so frequently, demonstrate technique with a spacer, ensure they are holding their breath for 10 seconds.
-Ensure they are washing their mouth after using a Clenil inhaler

Question 10

Why do most SABAs come in MDI form and most preventer therapies are DPI form?

Answer 10

Difficulty during an asthma attack to take a deep forceful breath in required required by DPI formulations
Particle size is smaller in MDI formulations meaning that, it is likely there will be reduced deposition in upper airways
I did think that most beta receptors are lower in the respiratory tract- smaller particles are more likely to reach the lower airways. Larger particles for preventers in DPI form are okay as receptors are higher up.

Question 11

Which groups of patients would an accuhaler be unsuitable and why?

Answer 11

Not suitable for under 4s
Those with severe COPD (due patients groups may not be able to breathe in strongly enough, assess COPD patients inspiratory flow rate)
Those with dexerity issues (may fail to prepare capsule loading)

Question 12

What are some of the common problems with accuhalers?

Answer 12

Not loading the capsule properly
Not breathing in strongly enough
Not piercing the capsule or over piercing it
Getting moisture into the mouthpiece
Tilting the accuhaler down causing the dry powder to fall out, must be held just horizontally
Must dose the inhaler afterwards
Must hold breath for ten seconds after

Question 13

Give two examples of Breezhalers.

Answer 13

Seebri (Glycopyrronium) and Ultribo breezehaler (Glycopyrronium and Indacaterol)

Question 14

What must you do after using a Breezhaler?

Answer 14

Empty the remains of the capsule shell afterwards

Question 15

What are some of the common problems associated with a Breezhaler?

Answer 15

Shaking the inhaler
Not piercing the capsule
Not using a new capsule for each dose
Not breathing in hard enough

Question 16

Which type of DPI requires the highest level of resistance?

Answer 16

Handihaler then
Turbohaler then
Accuhaler then
Breezhaler

Question 17

What inspiratory rate do DPIs require in comparison to MDIs?

Answer 17

DPIs require an inspiratory rate between 30-90 L/min whereas MDIs require an inspiratory rate between 20-60 L/min.

Question 18

What should you hear when you breathe in with a Handihaler and Breezhaler?

Answer 18

Vibrating noise- if you don’t hear it then check that capsule is pierced properly

Question 19

What is an example of a Handihaler?

Answer 19

Spiriva (Tiotropium)

Question 20

What are some of the common problems associated with Handihaler?

Answer 20

Overpiercing the capsule
Not breathing in strongly enough
Swallowing the capsule instead of inhaling it
Not taking a second breath to get the full dose
Not using a new capsule each time

Question 21

What are the two brand names associated with the Turbohalers?

Answer 21

Pulmicort or Symbicort

Question 22

What are the common problems associated with a Turbohaler?

Answer 22

Not holding it upright when loading the dose
Covering air inlets with lips
Breathing in the nose instead of the mouth
Shaking it to see how much is left
Can’t store it in a damp place with the lid off

Question 23

What are the benefits of using a nebuliser?

Answer 23

Patients do not need to worry about coordinating their breaths
No manual dexterity issues
Can supply oxygen at the same time

Question 24

What considerations must be made regarding the formulation of nebulisers?

Answer 24

-pH must match that of the lungs, any deviation may cause bronchospams. Buffer vehicles are used in order to do so.
-Hypo-osmotic or hyper-osmotic may cause bronchospams; salts are used to maintain tonicity.
-Due to the gradual evaporation of the solvent this causes a temperature decrease which may cause precipitation of the particles causing a bronchospams
-The lower the viscosity the higher the rate of atomisation; viscocity ensures an even distribution of particles size.
-Sterility of aqueous solution; manufactured under aseptic conditions.
-Surfactants can be used to increase solubility.
-Chemical preservatives are not recommended (sulphites may cause bronchospasm).

Question 25

Explain the main concept of nebulisers?

Answer 25

Nebulisers turn liquid medicine into a fine mist for easy administration.

Question 26

Explain the mechanism of air jet nebulisers.

Answer 26

In air jet nebulisers work on the concept of high pressure ‘jet stream’ of oxygen is forced into the solution. At the tip of the airstream nozzle negative pressure occurs forcing the particles upwards. Initially the particles are quite larger but as they travel upwards their surface area increases forming smaller droplets.

Question 27

How do ultrasonic nebulisers work?

Answer 27

Instead of pressurised air generating the aerosol droplets, instead there is a transducer which induces vibrations, particles at a higher energy form aerosol droplets.

Question 28

How do mesh nebulisers work?

Answer 28

Using vibrating crystals that are forced through a mesh generating aerosol particles with a high fine particle fraction.

Question 29

What is special about mesh nebulisers?

Answer 29

They can be fitted with an adaptive aerosol delivery system which enables the flow of particles to only be emitted during exhalation.

Question 30

Is lower or higher surface tension solutions better for nebulisers?

Answer 30

Lower surface tension solutions are generally easier to atomise and are therefore preferred.

Question 31

What are some of the formulation changes that occur in air jet nebulisation solution?

Answer 31

Temperature decreases by 10 to 15 degrees during air jet nebulisation. This can affect the solubility of the drug in addition to the viscosity and surface tension.
The drug concentration will increase causing again modifications to the viscosity and surface tension.

Question 32

What are some of the formulation changes that occur in ultrasonic nebulisation?

Answer 32

The temperatures increase by 10 to 15 degrees which causes changes to surface tension and viscosity.
Due to the temperature increase this causes the drug to denature.

Question 33

What are some of the practical aspects of formulation of nebulisers?

Answer 33

Nebuliser duration- need to nebulise to dryness
Dead volume- approximately 1mL