RX422: Inhalation Drug Delivery

What are the advantages of inhalation drug delivery?

Quick onset

Non-invasive

What makes inhalation drug delivery quick onset?

Large surface area

Limited first pass metabolism

Absence of extreme pH

Rich blood supply

What are the disadvantages of inhalation drug delivery?

Limited to potent low-dose drugs

What are the 3 parts of the airway?

Nasopharyngeal region

Tracheobronchial

Alveolar

What is brownian diffusion?

Smaller particle size - higher brownian motion

What part of the airway is affected by inertial impact?

Trachea and main bronchi

What size particle elicits its effects from inertial impact?

Bigger than 10 nanomicrons

What part of the airways are effected by gravitational settling (Sedimentation)?

Alveolar ducts and sacs

What are the downsides of inhalation particles larger than 10 nanomicrons?

Rapidly removed by coughing, swallowing, and mucus.

What particle size is predominantly deposited in the tracheobronchial region?

3-5 nanomicrons

What size particles deposit in the alveolar region?

particles less than 3 nanomicrons

What happens to particles inhaled that are smaller than 1 nanomicron?

Removed from the lung by exhaled air

What three pharmaceutical factors affect droplet / powder disposition?

Aerosol velocity

Size of droplet or powder

Physical stability in terms of particle size (Lipophilic v. hydrophilic)

What four physiological factors affect droplet / powder disposition?

Lung morphology (Disease)

Tidal volume

Disease state (Hyper secretion of mucus)

Bronchial circulation (Fibrosis)

What are metered dose inhalers?

Pressurized self-propelled aerosol device

What inhalers must be tested for terminal sterility?

Nebulizer

RESPIMAT / MDLI

What inhalers don’t need to be tested for terminal sterility?

MDIs

DPI

What happens to boiling point and vapor pressure in MDIs?

Vapor pressure increases as boiling point decreases

What are the advantages of spacers?

Reduced hand-breath-eye coordination

Reduced systemic and local side effects

Large drug doses delivered conveniently

What are the disadvantages of spacers?

Bulky / less portable

Expensive

Need cleaned

Unknown inhalation technique

Non-suitable for some canisters (Shape)

What goes into a formulation for MDI?

Propellant

Co-solvent

Surfactant

What type of propellant is used in MDI?

High vaporization pressure and low boiling point

What is the purpose of co-solvents in MDIs?

Solubilization of surfactant

Deflocculation of suspension

What is the purpose of surfactants in MDIs?

Wetting of suspension drugs

What can MDIs be formulated as?

Suspension or solution

What type of propellant is preferred?

HFO

How do you administer an MDI?

Prime before first use (Not needed after)

Shake before use

What are dry powder inhalers?

No propellant only dry product

How do dry powder inhalers work?

Inspiratory flow fluidizes the powder

What drug particle size can be used in DPIs?

1-3 nanomicrons

What excipient is used in DPIs? What is its purpose?

Lactose monohydrate

• Improves filing for low dose drug

  • Improves flow by reducing cohesive force to device

What is the most suitable product for DPIs?

Proteins and biologics

What is the therapeutic dose range for DPIs?

Less than 12 nanograms

What are the major limitations of DPI drug delivery?

Particles’ strong cohesive force

Patient' inability to achieve sufficient inspiratory flow

How do you administer DPIs?

No shaking

No priming

What do nebulizers do?

Convert aqueous solutions or micronized suspension of drugs into an aerosol

What are the 2 requirements for a solution to be used in nebulizers?

Low viscosity

Low surface tension

What populations benefit from nebulizers?

Geriatric and Pediatric patients

Have you drank water recently?

Drink 😐

How are nebulizers formulated?

Solution or micronized suspension

What are the things in nebulizers (What is it formulated with)?

Vehicle

Cosolvents

Preservatives / antioxidants

Buffers

What are cosolvents used for in nebulizers?

Solubilization of drugs

What must cosolvents be for nebulizers?

Low viscosity and surface tension

What must be true of a vehicle in nebulizers?

WFI - pH above 5

What is RESPIMAT or MDLI?

Aqueous solution or micronized suspension dispensed by micropump

What inhalers need to be primed?

RESPIMAT / MDLI

MDI

What are thermal vaporization aerosol devices?

Breath-actuated inhalation delivery system?

What must be true of drugs used in thermal vaporization aerosol devices?

Thermally stable

Low melting point