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dosage > EXAM 3 L4 > Flashcards

EXAM 3 L4 Flashcards

1
Q

Inhalation dosage forms

A

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

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2
Q

Local application

A

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

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3
Q

Systemic application

A

Rapid absorption
Fewer drug-metabolizing enzymes

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4
Q

Inhaled fluticasone properties

A

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

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5
Q

Systemic app. of inhaled meds

A

-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)

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6
Q

Aerodynamic diameter (Dae)

A

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)

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7
Q

Extrathoracic region properties

A

Airways in head and neck

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8
Q

Upper and Lower bronchial region properties

A

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

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9
Q

Alveolar region

A

Nonciliated thoracic airways and airspaces

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10
Q

Particle deposition mechanisms

A

Diffusional Transport
Inertial Transport
Gravitational Transport

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11
Q

Inertial Transport

A

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

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12
Q

Diffusional Transport

A

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

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13
Q

Gravitational Transport

A

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

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14
Q

Factors determining particle sedimentation

A

-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)

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15
Q
A
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16
Q

Particle with a unit density vs low density particle

A

Different geometric diameters, SAME aerodynamic diameters

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17
Q

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

A

True

18
Q

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

A

False, lower airways

19
Q

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

A

True

20
Q

Challenges in pulmonary drug delivery are due to

A

Due to the defense mechanisms of the lung

21
Q

Challenges in pulmonary drug delivery Upper (head) airways

A

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

22
Q

Challenges in pulmonary drug delivery conducting (lung) airways

A

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

23
Q

Challenges in pulmonary drug delivery in the alveoli

A

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

24
Q

Types of aerosols

A

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

25
Q

Propellant-driven (“pressurized”) metered-dose inhalers (pMDI):

A

-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

26
Q

pMDI needs….

A

Good inhalation technique (for children spacer needed)

27
Q

pMDI characteristics:

A

-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

28
Q

Components of pMDI

A

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

29
Q

Nebulizers

A

-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

30
Q

Jet Nebulizers

A

-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

31
Q

New Nebulizer properties

A

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

32
Q

Dry Powder Inhalers (DPI):

A

-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

33
Q

DPI devices

A

-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

34
Q

Single unit dose

A

Inhaler is smaller
Design is relatively simple

35
Q

Multiple unit-dose

A

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

36
Q

Particle production forms

A

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

37
Q

Jet milling

A

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

38
Q

Spray drying

A

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

39
Q

Particle interaction types:

A

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

40
Q

Particle deposition is influenced by:

A

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

41
Q

Carrier-based DPI formulations

A

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

42
Q

Aerosol performance depends on carriers properties:

A

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

dosage (30 decks)

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