Lecture 8: Formulation of medicines for the respiratory system Flashcards
What are the Pulmonary delivery devices used to generate an aerosol?
- Pressurised meter dose inhalers (pMDI)
- Dry powder inhalers (DPIs)
- Nebulisers
What are the most common active pharmaceutical ingredients delivered y aerosols?
- b2 agonists
- Anticholinergics
- Corticosteroids
What is the definition of an aerosol?
Colloidal systems consisting of very finely subdivided liquid or solid particles dispersed in and surrounded by a gas
What is the definition of an aerosol?
Colloidal systems consisting of very finely subdivided liquid or solid particles dispersed in and surrounded by a gas
Define Mass median aerodynamic diameter (MMAD)
Diameter at which 50% of the particles of an aerosol by mass are larger and 50% are smaller than the median diameter
Define Fine Particle Fraction (FPF)
Fraction of particles (< 5 micron diameter) that can achieve deposition in the lower respiratory tract
Define labelled dose
Dose that is metered and stated on device packaging e.g. Flixotide® 125 (125mcg fluticasone per actuation of inhaler)
Define Emitted dose
The mass of drug emitted per actuation that is actually available for inhalation at the mouth
What are the advantages of local treatment of respiratory disease
- Non-invasive and painless
- Delivers high drug concentrations directly to the disease site(s)
- Rapid clinical response
- Bypasses barriers to therapeutic efficacy e.g. poor GI absorption, first-pass metabolism
- Achieve similar or superior clinical effects with a fraction of a systemic dose e.g. 2 - 4mg salbutamol PO is equivalent to 100 – 200 mcg by pMDI
What are the disadvantages of local treatment of respiratory disease
- Administration techniques differ between and within device categories
- Less than optimal technique of device can therefore compromise therapeutic effect
- More patient training and time is required for effective drug administration
What are the five key components of a metred dose inhaler?
- Container
- Propellants
- Actuator
- Metering valve
- Formulation
What is the container of a metred dose inhaler made from and what are the advantages?
Aluminium
- Light
- Inexpensive
- Compact material
Why is the container of a metred dose inhaler made from alumium?
Prevents ingress of daylight (good for photostability)
Wha are the requirements of a container?
Must be able to withstand the high pressures generated by the propellant
What is the internal surface of a container of a metred dose inhaler coated with and why?
inert polymer to prevent interaction of the formulation with the container surface e.g. adhesion of drug particles in a suspension formulation
What is the actuator of a metred dose inhaler manufactured using?
plastic injection moulding techniques
What does the actuator house?
pMDI canister and has an inbuilt nozzle
What volume of the formulation does a metering valve deliver?
25 - 100 nL
What is the basic operating principle of metering valve?
- Prior to activation a channel between the container body and the metering chamber is open to allow formulation entry into dosing chamber
- As the pMDI is activated, this channel closes, and another channel connecting the metering chamber to the atmosphere opens
- The pressurized formulation is expelled rapidly into the valve stem, which, together with the actuator expansion chamber allows the propellant to start to boil resulting in the production of an aerosol plume
How is the metering valve used?
The canister is used in the inverted position, with the valve below the container to allow valve filling under gravity
Some valves are surrounded by a retaining cup that contains a few doses of drug
What can impact upon aerosol particle size distribution and subsequent lung distribution?
The actuator polymer and the nozzle design