EXAM 3 L4

Question 1

Inhalation dosage forms

Answer 1

For local (asthma, COPD, lung infections) and systemic (diabetes) applications

Question 2

Local application

Answer 2

High local concentration
Fast Action at the site if pulmonary diseases
Lower systemic side effects

Question 3

Systemic application

Answer 3

Rapid absorption
Fewer drug-metabolizing enzymes

Question 4

Inhaled fluticasone properties

Answer 4

Oral admin of fluticasone has bioavailability <1% because of first-pass effect
Plasma protein binding is more than 99% - less than 1% of drug available.
Systemic admins. cause sever side effects (HYPERCORTICISM)
-Has absolute bioavailability ~10% and is safe for children > 1 yr old

Question 5

Systemic app. of inhaled meds

Answer 5

-Human lungs have 300-500 alveoli
-Big SA: 500-10000 feet squared
-Alveoli surrounded by lung capillaries
-Alveoli have very thin cell walls for gas exchange (good for absorption)

Question 6

Aerodynamic diameter (Dae)

Answer 6

Geometric diameter of a particle with a unit mass density (1 g/cm^3) that would settle at the same velocity as the particle of interest
(Dae = (PpDgeo)

Question 7

Extrathoracic region properties

Answer 7

Airways in head and neck

Question 8

Upper and Lower bronchial region properties

Answer 8

-Upper - Trachea and bronchi (large ciliated thoracic airways)
-Lower - Bronchioles (small, ciliated thoracic airways)

Question 9

Alveolar region

Answer 9

Nonciliated thoracic airways and airspaces

Question 10

Particle deposition mechanisms

Answer 10

Diffusional Transport
Inertial Transport
Gravitational Transport

Question 11

Inertial Transport

Answer 11

-(Impaction)
-Driven by momentum
-Increase with particle velocity, diameter, density
-Extrathoracic region

Question 12

Diffusional Transport

Answer 12

Ultrafine particles (<0.1 nanometer)
Lung periphery (alveoli)
Tend to be exhaled without depositing
Alveolar region

Question 13

Gravitational Transport

Answer 13

(Sedimentation)
Particles >0.1nanometer
Increase with diameter and density
Bronchial region; alveolar region

Question 14

Factors determining particle sedimentation

Answer 14

-VT: Terminal setting velocity
-p: density of particles
-g: acceleration due to gravity
-D: volume Diameters
-CD: Slip correction factors (insignificant for >1nano m)
-k: Shape factors (fibers, elongated particles, needles, spheres)
n: Viscosity of fluid (air)

Question 16

Particle with a unit density vs low density particle

Answer 16

Different geometric diameters, SAME aerodynamic diameters

Question 17

T/F: In pulmonary drug delivery system, particles with aerodynamic diameter >5 nm will normally deposit in upper airways due to inertial impaction

Answer 17

True

Question 18

T/F: Particles with aerodynamic diameter 1-5 nm will mostly deposit in upper airways

Answer 18

False, lower airways

Question 19

T/F: Particles with aerodynamic sizes < 1 nm may be exhaled

Answer 19

True

Question 20

Challenges in pulmonary drug delivery are due to

Answer 20

Due to the defense mechanisms of the lung

Question 21

Challenges in pulmonary drug delivery Upper (head) airways

Answer 21

-Filtering mechanisms in the nasal cavity trap and eliminate large particles (>10nm)
-Reflexes: sneezing and coughing

Question 22

Challenges in pulmonary drug delivery conducting (lung) airways

Answer 22

-Mucociliary escalator
IgA (an antibody produced by plasma cells in the submucosa)

Question 23

Challenges in pulmonary drug delivery in the alveoli

Answer 23

-Alveolar macrophages
-Immunologic mechanisms: T & B lymphocytes; IgG

Question 24

Types of aerosols

Answer 24

-Liquid droplets
Pressurized metered-dose inhalers (pMDIs)
Nebulizers
-Dry particles
Dry powder inhalers (DPIs)

Question 25

Propellant-driven ("pressurized") metered-dose inhalers (pMDI):

Answer 25

-A small volume of pressurized drug dispersion is isolated in a metering chamber and then released through a spray orifice -As the released drug dispersion begins to equilibrate with the atmospheric pressure, it is propelled from the container forming a spray of droplets

Question 26

pMDI needs....

Answer 26

Good inhalation technique (for children spacer needed)

Question 27

pMDI characteristics:

Answer 27

-Need good inhalation technique -Lung deposition efficiency is typically low: 5-20% -High droplet velocity leads to extensive deposition of drug in the oral areas (up to 80%) -Drug/Solvent compatibility issues with the propellant -Only suitable for low-dose meds -Less expensive

Question 28

Components of pMDI

Answer 28

-Drug -Propellant Chlorofluorocarbon (CFC) Hydrofluoroalkanes (HFA) -Cosolvent Ethanol -Surfactant Sorbitan trioleate, oleic acid, lecithin

Question 29

Nebulizers

Answer 29

-Generate droplets of a drug dispersion (usually aqueous solution or suspension) using energy from compressed air or piezoelectric ceramics -Delivered to the patients' lungs on their inspiratory flow -Suitable for treatment of young and elderly patients and emergency treatment

Question 30

Jet Nebulizers

Answer 30

-Traditional jet nebulizers are more time-consuming than pMDIs or DPIs -Require hygienic maintenance of the equipment -Traditional jet nebulizers are bulky -Traditional jet nebulizers are low efficiency with only 10-15% of drugs deposited in the lungs

Question 31

New Nebulizer properties

Answer 31

-Smaller than traditional jet nebulizers -Higher delivery efficiency -Lower residues -New types: Vibration mesh nebulizer Soft mist inhaler

Question 32

Dry Powder Inhalers (DPI):

Answer 32

-Collection of dry particles contained in an inhaler device or loaded into the device prior to use -An aerosol of dry powder is created by airflow, which then carries the small drug particles to the lung -Depending on the performance of formulation, device and airflow, the dose deposited in the lung ranges 5-40% -Asthma, COPD, lung infections -Insulin DPIs

Question 33

DPI devices

Answer 33

-Breath-actuated passive devices Powder aerosols are generated by patients' inspiratory airflow Performance of a device could be highly variable among patients -Power-assisted active devices Mechanical or electrical external energy generates powder aerosols Less dependent on patient's capability

Question 34

Single unit dose

Answer 34

Inhaler is smaller Design is relatively simple

Question 35

Multiple unit-dose

Answer 35

-Convenient for frequent use -Inhaler is larger -Design is relatively complex

Question 36

Particle production forms

Answer 36

-Mechanical milling: applying mechanical forces to break coarse particles -Jet milling: used in pharm. industry to produce inhalable drug particles -Spray drying

Question 37

Jet milling

Answer 37

-Jet milled particles are typically COHESIVE WITH HIGH SURFACE ENERGY and HIGH ELECTROSTATIC CHARGE -Poor flowability and poor aerosolization

Question 38

Spray drying

Answer 38

Drug is dissolved in a solvent, atomized into small droplets, and dried by hot airflow through solvent evaporation

Question 39

Particle interaction types:

Answer 39

-Van Der Waals forces -Electrostatic interactions (significant for some materials at dry conditions) -Capillary forces (Significant for hygroscopic particles at high humidity) -Mechanical Interlocking

Question 40

Particle deposition is influenced by:

Answer 40

-Particle geometric diameter -Density -Morphology -Surface energy -Electrostatic charge -Hygroscopicity

Question 41

Carrier-based DPI formulations

Answer 41

-Carriers act as a filler for low-dose drugs -Improve flowability

Question 42

Aerosol performance depends on carriers properties:

Answer 42

-Particle geometric diameter -Morphology -Surface energy -Electrostatic charge -Drug to carrier ratio -Addition of additives