Inhalational preparations

Question 1

Site of action of Inhalational drugs:

Answer 1

Inhalational drugs can work locally in the lungs but also systemically

Question 2

How is the delivery into deeper parts of the lungs accomplished?

Answer 2

(20-50 µm: localized effects in trachea)

-smaller particle size 5-19 µm: respiratory bronchioles
-< 5 µm: alveolar ducts & alveoli; but they are so small that subject to exhalation -> so not preferred for the lung delivery

Question 3

How do droplets settle in the lungs - Inertial impaction

Answer 3

Inertial impaction is the effect that causes the bigger particles to settle in the upper airway

20-50: bigger particles, will bump into the turbulent and narrow upper airways, the size causes them to settle there

5-19: settle via sedimentation in the bronchioles
< 5: may not be deposited due to Brownian motion

Question 4

What are the barriers of the Inhalation route?

Answer 4

-Upper airway: Cilia and mucus pushing insoluble substances out

-in the alveoli: insoluble small particles are phagocytosed by macrophages

-> these barriers can be impaired in sick patients

Question 5

What advantages of Inhaled drugs?

Answer 5

Pros:
-Rapid onset
-Reduced dosage & side effects: because the liver is passed the dose is less and it stays locally
-avoid the first metabolism

Question 6

Why do the Aerosols look like fine mist upon activation?

Answer 6

Drug + Propellent (is under pressure in the device) + Excipient
upon activation, the propeller vaporizes and turns the formulation into a fine mist -> liquid or solid droplets surrounded by gaseous medium

Question 7

What are the advantages of Aerosols:

Answer 7

-Noncontaminating packaging -> Hermetic container (airtight)
-Ease of application of a uniform thin layer
-Application without touching the affected area
-Particle size control
-dose uniformity
-efficacy can be altered

-> work topically, intravaginal, rectal

Question 8

Explain the principle of Aerosol formation:

Answer 8

The container contains a mixture of propellant and drug
-propellant = liquified gas with much higher pressure than the atmospheric pressure at room temperature

-upon actuation, the pressure forces the liquid to move up the dip tube and out of the valve -> propellant vaporizes to break the formulation into a fine mist

Question 9

What is a Propellant?

Answer 9

-propellant = liquified gas with much higher pressure (15-70 psig higher) than the atmospheric pressure at room temperature

-Low toxicity
-Chemically inert
-Nonflammable / non-explosive
-Free from odor and color
-Good solvent power
-Free from irritation
-Practical cost

Types: Fluorocarbons, Hydrocarbons, Compressed gas

Question 10

Why was the Aerosol CFC banned?

Answer 10

Chlorofluorocarbons (CFC) were banned because the Chlorine reacted with Ozone causes its depletion -> increase of UV exposure -> more skin cancer

Question 11

Types of Propellants: Phase systems

Answer 11

-Two-Phase System: Vapour phase (propellant), Liquid phase (propellant and product) surface spray

-Three-Phase System: Vapour, Liquified Vapour, Product (not miscible with propellant) -> Water-based aerosols or Foams

Compressed Gas: compresses gas propellant without a liquid phase -> solid stream. wet spray, foam

Question 12

Container material of aerosols:

Answer 12

-Glass and Plastics (can’t handle high pressure)
-Steel and Aluminium

Question 13

What is the Filling process for Aerosols?

Answer 13

-Cool filling: the product must be cooled to -40°F and filled into a cooled container -> Cool and propellant

-Pressure filling: Product is added to the device, the valve is attached -> liquified gas is added under pressure

Question 14

Types of Aerosol devices:

Answer 14

-Liquid Inhalers, the product is liquid: Metered Dose Inhalers (MDI or pMDI) -> the valve is metered, uniform dose with each activation
->timing: pressing when inhaling, a spacer will cause the medication to take more time to get to the patient’s throat, so the timing must not be perfect

Nebulizers for geriatrics and pediatrics -> drug in liquid but no propellants, an air stream is used to form the particles, and no timing when inhaling is needed

-Powder Inhalers, product in powder form
-Others

Question 15

What are Dry powder inhaler (DPI)?

Answer 15

• Stable dry-powder formulations, no propellent, instead the patient’s breath is needed for activation (aerosolization)
• Risk of microbial growth is lower for solids
• Can deliver drugs to the deep lung
• 1-3 puffs are sufficient because aerosol particles contain drugs in a very concentrated form

Question 16

DPI Examples:

Answer 16

-Afrezza® inhalation powder, a rapid-acting insulin
-> Insulin adsorbed on Technosphere microparticles

-Spinhaler, a powdered drug in a hard gelatin capsule
breath intake moves rotor -> aerosolizing the powder

Question 17

What are some instructions for Aerosal use?

Answer 17

-Slow and deep inhalation
-hold your breath for 10 seconds (to prevent exhalation of the drug)
-Spacer devices: increases aerosolization and decreases need for synchronization

Auxiliary Label:
-contents under pressure
-Do not puncture or expose to heat
-keep away from children