PH2107 - Inhalers 2

Question 1

What is an Active Inspiromatic?

Answer 1

An active DPI

• fine drug at low flow rate
• micro pump de-agglomerates the powder via a vortex
• patient inhalation monitoring
• microcontroller to calculate optimal time for drug delivery
• built in real-time feedback interface
• automatic data logger

Question 2

What factors influence aerosol characteristics?

Answer 2

• inhaler resistance
• patient characteristics
• formulation variables
• inhaler design

Question 3

What are the criteria for an ideal DPI?

Answer 3

• generate an aerosol with most of the drug carrying particles less than 5 um in size (ideally 0.5 - 3 um)
• give reproducible drug dosing
• be readily used by the patient with minimal training
• protect the physical and chemical stability of the drug
• be relatively portable and inconspicuous during use

Question 4

What are the advantages of using a DPI?

Answer 4

• quick and convenient to use
• usually compact and portable
• no “press and breathe co-ordination” required in passive DPIs
• no propellants needed
• can often deliver larger doses than pMDIs
• DPIs often viewed as more modern technology

Question 5

What are the disadvantages of using a DPI?

Answer 5

• unit dose DPI relatively inconvenient
• aerosol formation in passive DPIs depends on inspiratory effort
• retail cost may be greater than pMDIs
• powder may be moisture-sensitive
• potential for delivered dose content uniformity problems in multidose DPIs
• potentially confusing range of novel devices

Question 6

What is a pMDI?

Answer 6

Pressurised Metered Dose Inhalers

Question 7

How do pMDIs deliver formulation in a form of an aerosol?

Answer 7

• patient presses can which opens channel between metering chamber and atmosphere
• propellants start to boil in expansion chamber
• shearing forces produce ligaments
• propellant droplets form at actuator nozzle (2-phase gas-liquid air-blast)
• initial velocity 30/ms
• initial droplet size 20 - 30 um
• evaporation and cooling of particles

Question 8

What important considerations are there for drug delivery using a pMDI?

Answer 8

• uniform drug distribution within the metering chamber and container
• smooth movement of the valve stem during actuation
• good sealing to provide an accurate volume/dose delivery
• no drug/formulation retained after dose delivery

Question 9

What are the formulation characteristics of a pMDI?

Answer 9

• consistent product performance through can life
• uniform formulation ensuring accurate and consistent doses
• drug suspension stabilised as loose agglomerates and readily re-dispersed upon shaking
• no particle or crystal growth to ensure aerosol performances
• no drug loss due to absorption onto canister surfaces
• protection from moisture ingress to ensure long term stability

Question 10

Describe the suspension formulation in a pMDI

Answer 10

• micronized drug particles suspended in liquefied propellant
• may contain surfactant and co-solvent to aid suspension
• chemically stable
• physical stability
• suspension pMDI (e.g. Clenil modulate)

Question 11

Describe the solution formulation in a pMDI

Answer 11

• drug dissolved in liquefied propellant
• may contain surfactant and co-solvent to dissolve the drug
• excellent dose reproducibility
• fine spray/high throat deposition
• limited to high potency or highly soluble drugs
• solution pMDI (e.g. QVAR)

Question 12

What is the function of surfactants in a pMDI?

Answer 12

• stabilise suspension formulations
• minimise drug deposition on inner surface
• excess can result erratic delivered dose
• compact sedimentation
• creaming

Question 13

What is a propellant in a pMDI?

Answer 13

Liquefied compressed gases that are in the gaseous phase at atmospheric pressure, but form liquids when compressed

Question 14

What are the requirements for propellants in pMDI?

Answer 14

• non-toxic
• non-flammable
• compatible with drugs formulated
• have appropriate boiling points and densities
• the vapour pressure must be constant throughout the product’s life

Question 15

Give three examples of CFCs used in pMDIs

Answer 15

• dichlorodifluoromethane (CFC-12)
• trichlorofluoromethane (CFC-11)
• dichlorotetrafluoroethane (CFC-114)

Question 16

What is the vapour pressure inside a pMDI?

Answer 16

300 - 500 kPa (3 - 5 atmospheres) depending on the propellant mixture, other excipients (surfactants etc) and ambient temperature

Question 17

What is the Montreal Protocol?

Answer 17

Recognizing that world-wide emissions of certain substances can significantly deplete and otherwise modify the ozone layer in a manner that is likely to result in adverse effects on human health and the environment

Question 18

What is an HFA?

Answer 18

Hydrofluoroalkanes

Question 19

What has the reformation of pMDIs with HFA propellants led to?

Answer 19

Many challenges involving the development of new

• excipients
• metering valves
• filing methods
• toxicity testing
• clinical testing

Question 20

What is the function of the valve in a pMDI?

Answer 20

• sealing mechanism to retain volatile formulation
• barrier to moisture ingress
• accurate and reproducible metering i.e. delivered dose

Question 21

What is the metering volume of a pMDI?

Answer 21

Typically

• 25 ul
• 50 ul
• 63 ul
• 100 ul

Question 22

What are two types of valves in pMDIs?

Answer 22

• retention valves

- primeless valves (i.e. fast fill/fast drain)

Question 23

What is the function of the seal in a pMDI?

Answer 23

• an elastomeric material is placed around a moving stem to seal the formulation within a chamber
• during the movement of the stem the seal is subjected to friction, increasing the deformation of the sealing area

Question 24

what is the effect of a deformed seal in a pMDI?

Answer 24

• valve leakage
• drug absorption
• dose variability changes
• “loss of dose” and “loss of prime” effects

Question 25

What is the cannister made from in a pMDI?

Answer 25

Aluminium
- bare aluminium
- anodised aluminium
- coated aluminium
- polymer coating
- heat cured e.g. fluoropolymers - PTFE, FEP, PFA
- plasma
- gaseous monomer e.g. fluoro, carbon etc
Stainless steel

Question 26

What is the function of the actuator in a pMDI?

Answer 26

Mechanism to fire the inhaler
Mouthpiece/patient interface
Control aerosol spray behaviour
- spray pattern
- plume geometry

Question 27

What is the actuator made from in a pMDI?

Answer 27

Polypropylene

Question 28

Give examples of methods of preserving food and water

Answer 28

• heating
• drying
• smoking
• salting
• acidifying
• impregnating with spices and aromatics

Question 29

Give examples of methods of preserving materials

Answer 29

Mummification
Timber (olive oil)
Paints
Plastics

Question 30

Which pharmaceutical products need a preservative?

Answer 30

• sterile and non-sterile preparations
• parenteral, ophthalmic, oral, topical, otic (BP) preparations
• cosmetics

Question 31

What is the purpose of preservatives in pharmaceutical preparations?

Answer 31

• prevention of microbial spoilage of products and decreasing risk of infection when the preparation is administered
• preservatives should prevent the proliferation of micro-organisms in non-sterile products
• preservatives should kill micro-organisms in sterile products

Question 32

Which pharmaceutical products are self-sterilising?

Answer 32

• products containing more than 15% alcohol (elixirs, spirits, tinctures)
• products containing a high concentration of sugar (>85%) syrups (exosmotic effect)
• products containing a high concentration of sugar (<85%) AND sufficient polyol (sorbitol, glycerin, propylene glycol)