Pulmonary Drug Delivery

Question 1

What are pharmaceutical aerosols?

Answer 1

Pharmaceutical aerosols are aerosol products containing pharmacologically active ingredients dissolved, suspended or emulsified in a propellant or a mixture of solvent and propellant, and intended for administration orally as fine solid particles or liquid mists through the pulmonary airways, or for administration into one of the body cavities (nose, rectum, vagina), or for topical administration to the skin

Question 2

What are the advantages to pharmaceutical aerosols?

Answer 2

Drugs that are usually given parenterally can be given by inhalation
Rapid onset of action, less degradation in the GI tract and less first pass metabolism
Accurate dosing and potential to tailor doses to meet the individual patient’s needs
No risk of contamination
Less drug irritation with topical application

Question 3

What are some drug characteristics necessary for aerosol development?

Answer 3

No irritation to drug absorption site
Be reasonably soluble in respiratory fluids
Be therapeutically effective at a relatively low dose
Exhibit passive drug transport mechanism through respiratory membranes
Be stable and compatible with propellants and have a pH between 5.5 and 7.5

Question 4

How does absorption change throughout the airways (central airways vs alveolus)?

Answer 4

The rate of absorption of a compound from the alveolus is approximately two times faster than in the central airways, suggesting greater membrane permeability in alveolus than in tracheobronchial region

Question 5

What happens to a drug in the central airways?

Answer 5

A drug may:

• interact with the mucus layer
• be removed by the mucociliary escalator
• have limited access through the epithelium, interact with epithelium-associated components
• be removed by diffusion into the submucosal blood vessels
• reach the smooth muscle cells

Question 6

What happens to a drug in the alveolus?

Answer 6

A drug may:

• be diluted/diffused laterally in surfactant
• be taken up by alveolar macrophages
• diffuse through the interstitium and be removed by lymphatic capillaries
• be biotransformed by enzymes
• reach in blood circulation

Question 7

What is one of the most important factors that can influence drug absorption and bioavailability in the lungs?

Answer 7

Drug deposition in the airways

Question 8

How does breathing affect drug deposition?

Answer 8

Rapid, shallow inspiration promotes central deposition of a drug
Slow, deep inspiration leads to peripheral airway deposition
Holding breath at the end of inspiration of an aerosol facilitates drug deposition through sedimentation and diffusion

Question 9

How can adjusting the formulation improve drug deposition?

Answer 9

Using a spacer device
Reducing particle size and size distribution
Increasing drug density
Controlling hygroscopic growth of particles

Question 10

What are the 3 components that aerosols rely on?

Answer 10

Propellants
Valves/actuators
Containers

Question 11

What is a propellant?

Answer 11

A liquefied gas with a vapour pressure greater than atmospheric pressure at a temperature of 40*C

Question 12

What are the most common propellants used for oral or nasal inhalation S?

Answer 12

Dichlorodifluoromethane (Propellant 12)
Trichloromonofluoromethane (Propellant 11)
Dichlorotetrafluoroethane (Propellant 114)

Question 13

What are the most commonly used propellants for topical aerosols?

Answer 13

Hydrocarbons (butane, isobutene, pentane)
Also nitrogen (sometimes)

Question 14

What is the role of the valve/actuator?

Answer 14

The aerosol valve must be capable of delivering the drug content in the desired form

Question 15

What are the two types of valves?

Answer 15

The upright use valve

The inverted use valve

Question 16

What are the most commonly used containers?

Answer 16

Glass
Stainless steel
Aluminum

Question 17

What are solution aerosols?

Answer 17

Solution aerosols consist of therapeutically active ingredients in pure propellant, or a mixture of propellant and solvents

Question 18

What are the most commonly used co-solvents in solution aerosols?

Answer 18

Ethanol (most common)
Polyethylene glycol
Dipropylene glycol
Ethyl acetate
Hexylene glycol
Aceton
Glycol ethers

Question 19

What factors need to be taken into account when developing solution aerosols?

Answer 19

Effect of solvent-propellant blends on the solubility and stability of the active ingredients
Particle size and the surface tension of the droplets
Irritation potentials of various additives such as antioxidants and preservatives
Esophageal irritability of the formulation
Toxicity and pharmacological activity of all solubilizing agents

Question 20

Why do we formulate suspension aerosols instead of solution aerosols?

Answer 20

For medications that are insoluble in the propellant or propellant-solvent mixture, or when a co-solvent is not desirable

Question 21

What are some problems with formulating suspension aerosols?

Answer 21

Caking
Agglomeration
Particle size growth
Clogging of the valve

Question 22

What are important factors to consider when formulating a suspension aerosol?

Answer 22

Active and inactive components must be essentially anhydrous (or made anhydrous)
Maintain particle size and size distribution
Drug solubility (solubility should be minimal in propellants, but good in body fluids)
Dispersion agents should be nontoxic, biodegradable and minimally irritating to the respiratory tract

Question 23

What are some surfactants used for oral inhalations?

Answer 23

Polysorbates and sorbirtan esters
Lecithin derivatives
Oleyl alcohol and ethanol

Question 24

What are emulsion aerosols composed of?

Answer 24

Emulsion aerosols are composed of active ingredients, aqueous or a non-aqueous vehicle, surfactant and propellant

Question 25

Which phase is the propellant found in?

Answer 25

Since the propellant is generally insoluble, it can be in either the internal or external phase

Question 26

What are emulsion aerosols used for?

Answer 26

Emulsion aerosols are normally for external usage (especially on skin surface)

Question 27

What do edible foams consist of?

Answer 27

Active ingredients dissolved or suspended in a vegetable oil and emulsified with a food-grade emulsifier, such as glyceryl monostearate

Question 28

What are some other emulsifiers for emulsion aerosols?

Answer 28

Mostly non-ionic surfactants, including:

• polyoxyethylene fatty esters
• polyoxyethylene sorbirtan esters
• alkyl phenoxy ethanols
• fatty acid esters
• alkanolamides

Question 29

What are aerosols?

Answer 29

Aerosols are products that depend on the power of a compressed or liquefied gas to expel contents from the container