PH2107 - Inhalers 2 Flashcards
What is an Active Inspiromatic?
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
What factors influence aerosol characteristics?
- inhaler resistance
- patient characteristics
- formulation variables
- inhaler design
What are the criteria for an ideal DPI?
- 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
What are the advantages of using a DPI?
- 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
What are the disadvantages of using a DPI?
- 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
What is a pMDI?
Pressurised Metered Dose Inhalers
How do pMDIs deliver formulation in a form of an aerosol?
- 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
What important considerations are there for drug delivery using a pMDI?
- 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
What are the formulation characteristics of a pMDI?
- 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
Describe the suspension formulation in a pMDI
- 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)
Describe the solution formulation in a pMDI
- 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)
What is the function of surfactants in a pMDI?
- stabilise suspension formulations
- minimise drug deposition on inner surface
- excess can result erratic delivered dose
- compact sedimentation
- creaming
What is a propellant in a pMDI?
Liquefied compressed gases that are in the gaseous phase at atmospheric pressure, but form liquids when compressed
What are the requirements for propellants in pMDI?
- 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
Give three examples of CFCs used in pMDIs
- dichlorodifluoromethane (CFC-12)
- trichlorofluoromethane (CFC-11)
- dichlorotetrafluoroethane (CFC-114)
What is the vapour pressure inside a pMDI?
300 - 500 kPa (3 - 5 atmospheres) depending on the propellant mixture, other excipients (surfactants etc) and ambient temperature
What is the Montreal Protocol?
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
What is an HFA?
Hydrofluoroalkanes
What has the reformation of pMDIs with HFA propellants led to?
Many challenges involving the development of new
- excipients
- metering valves
- filing methods
- toxicity testing
- clinical testing
What is the function of the valve in a pMDI?
- sealing mechanism to retain volatile formulation
- barrier to moisture ingress
- accurate and reproducible metering i.e. delivered dose
What is the metering volume of a pMDI?
Typically
- 25 ul
- 50 ul
- 63 ul
- 100 ul
What are two types of valves in pMDIs?
- retention valves
- primeless valves (i.e. fast fill/fast drain)
What is the function of the seal in a pMDI?
- 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
what is the effect of a deformed seal in a pMDI?
- valve leakage
- drug absorption
- dose variability changes
- “loss of dose” and “loss of prime” effects
What is the cannister made from in a pMDI?
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
What is the function of the actuator in a pMDI?
Mechanism to fire the inhaler Mouthpiece/patient interface Control aerosol spray behaviour - spray pattern - plume geometry
What is the actuator made from in a pMDI?
Polypropylene
Give examples of methods of preserving food and water
- heating
- drying
- smoking
- salting
- acidifying
- impregnating with spices and aromatics
Give examples of methods of preserving materials
Mummification
Timber (olive oil)
Paints
Plastics
Which pharmaceutical products need a preservative?
- sterile and non-sterile preparations
- parenteral, ophthalmic, oral, topical, otic (BP) preparations
- cosmetics
What is the purpose of preservatives in pharmaceutical preparations?
- 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
Which pharmaceutical products are self-sterilising?
- 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)
