Term
| When is nasal delivery recommended? |
|
Definition
1. For local action
2. If systemic activity is needed but conventional routes are inappropriate
3. Targeted delivery to the brain
4. Immunization |
|
|
Term
| List the physiologic structures air pass through |
|
Definition
1. External naris
2. Choncha
3. Nasop harnyx (to trachea)
Only 12-14 centimeters through |
|
|
Term
| Define the olfactory region |
|
Definition
| Area with small capillaries and nerves directly connected to the brain |
|
|
Term
| List advantages to nasal route of administration |
|
Definition
-Ease of administration, non invasive
-Rich vasculature
-Rapid absorption and onset of action
-Possibility of bypassing metabolism
-Reduction of systemic side effects
-Rate and extent of absorption and plasma levels similar to IV administration |
|
|
Term
| List disadvantages of nasal administration |
|
Definition
-Small site for absorption
-Mucociliary clearance
-Potentially short residence time
-Low bioavailability
-Need for formulary enhancers
-Nasal irritation |
|
|
Term
| What is the volume of the human nasal cavity? |
|
Definition
| 16cm^3 (very small, when compared to the gut) |
|
|
Term
| What two types of formulation enhancers can be added to a nasal drug? |
|
Definition
-Absorption enhancers
-Mucoadhesives |
|
|
Term
| List pathologies a nasal ROA can treat locally |
|
Definition
-Seasonal allergic rhinitis
-Pruritus
-Sinusitis
-Rhinorrhea
-polyps |
|
|
Term
| What systemic drugs can be administrated by nasal ROA? |
|
Definition
-Analgesics
-Hormones
-Cardiovasculars
-Diabetic (poor)
-Sexual dysfunction
-Smoking cessation aids
-Obesity
-Vitamins |
|
|
Term
| How does nasal ROA get through the blood brain barrier? |
|
Definition
It doesn't need to; it bypasses it
Often along neural pathways |
|
|
Term
| What is the most common nasal dosage form? |
|
Definition
| Solutions, especially in spray pumps |
|
|
Term
What is the best droplet size to use for nasal ROA?
What is the most common droplet size from a spray or nebulizer? |
|
Definition
Optimal size: 20-40μm
Average spray size: more than 50μm
Average nebulizer size: less than 5μm |
|
|
Term
What happens when nasal drops are too large?
What happens when nasal drops are too small? |
|
Definition
Too large- go in the throat and gets smaller
Too small- goes into the lungs and can cause problems |
|
|
Term
| What can affect actuation of a device? |
|
Definition
-Patient coordination/education
-Hard ergonomics (user-friendliness) |
|
|
Term
| List three new advances in nasal delivery |
|
Definition
-More efficient, single use sprays
-Site actuator (controlled dispersion technology)
-Optinose (uses exhalation to close nasal cavity) |
|
|
Term
|
Definition
| A new bioadhesive added to nasal ROA, already in use |
|
|
Term
| Why is the nose a good place for immunizations? |
|
Definition
–A large number of viruses enter via the respiratory tract
–Nasal associated lymphoid tissue (NALT)
–Immunization to mucosa (IgA)
–Low enzymatic activity in the nose |
|
|
Term
| Which pathogen has an intranasal vaccine on market? |
|
Definition
|
|
Term
| List two common aerosol misconceptions |
|
Definition
Aerosols are not always canned/compressed
Aerosols are not always MDIs |
|
|
Term
|
Definition
| A dispersion of particles or droplets suspended in gas or vapors |
|
|
Term
| List advantages of aerosols |
|
Definition
-Local delivery, avoids metabolism
-Avoids systemic effects
-Rapid onset
-No food interactions
-Patient preferred to injection
-Large alveolar surface area |
|
|
Term
| List columnar epithelial cell types in the human bronchi |
|
Definition
-Ciliated cells
-Goblet cells (secrete mucus)
-Basal cells
-Brush cells |
|
|
Term
| What is a major limitation to pulmonary ROA? |
|
Definition
Lungs are designed to prevent exogenous compounds (ROA may be considered inefficient)
Some devices only deliver around 10% of dose |
|
|
Term
What size of particle is needed to reach the
a) Alveolar region
b) Bronchiolar region
c) Nasopharingeal region
? |
|
Definition
a) 1-5μm: Alveolar region
b) 5-10μm: Bronchiolar region
c) 10-30μm: Nasopharingeal region |
|
|
Term
| Define aerodynamic diameter |
|
Definition
"The ability of the particle to fly in a stream of air"
An expression of a particle's aerodynamic behavior as if it were a perfect sphere with unit-density and diameter equal to the aerodynamic diameter |
|
|
Term
| For particles greater than five μm, list the mechanisms of aerosol deposition |
|
Definition
1. Electrostatic interaction
2. Interception
3. Impaction |
|
|
Term
| For particles greater than five μm, list the mechanisms of aerosol deposition |
|
Definition
1. Gravitational settling (sedimentation)
2. Brownian diffusion |
|
|
Term
| Why do we counsel a patient to try to hold their breath after using an aerosol? |
|
Definition
-Because sedimentation/brownian diffusion takes a few minutes
-To prevent exhalation of drug |
|
|
Term
| If there is a broad distribution of particle size, describe the types of particles are that most likely |
|
Definition
Broad distributions around a mean have less small particles and more large ones by mass
So less efficient in alveolar drugs
Also, keep in mind particles aggregate or get put into droplets |
|
|
Term
| Give the formula for aerodynamic diameter |
|
Definition
dae=dgρ1/2
dae=aerodynamic diameter
dg=geometric diameter
ρ1/2=density |
|
|
Term
| How does solubility or hygroscopicity of a respiratory drug affect deposition? |
|
Definition
| If they are solubilized in the humid respiratory tract, the large droplets won't go as deep |
|
|
Term
|
Definition
-Oldest aerosol generating device
-Pediatric, geriatric, hospital use
-Air jet or ultrasonic |
|
|
Term
| What factors control nebulizer droplet size? |
|
Definition
–Volume of the solution
–Surface tension
–Density AND viscosity
–Nebulizer make / model
**Nebulizer model choice should be based on drug AND concentration |
|
|
Term
| List advantages of nebulizers |
|
Definition
-Long treatment times
-Aqueous solution (easy/environmentally friendly to manufacture)
-Does not depend on inspiratory force |
|
|
Term
| List disadvantages of nebulizers |
|
Definition
-Bulky
-Expensive
-Poorly optimized
-Contamination |
|
|
Term
| What is the main difference between an air jet and ultrasonic nebulizer? |
|
Definition
An ultrasonic nebulizer does not depend on an air source, it instead uses a piezoelectric transducer
However, it gets hot (drug damaging) and isn't popular. |
|
|
Term
|
Definition
| Metered Dose Inhaler that contains a pressurized metered dose that is aerosolized through an atomization nozzle |
|
|
Term
| What factors control particle size for an MDI? |
|
Definition
–The formulation
–The valve design
–The actuator
–The propellant |
|
|
Term
| List advantages of an MDI |
|
Definition
-Portable
-Perceived as easy to use and convenient
-Stability (protect from light, oxygen, and water)
-Tamper proof |
|
|
Term
| List disadvantages of MDI |
|
Definition
-Expensive
-Prone to incorrect use
-If punctured, pressurized contents are a safety issue |
|
|
Term
|
Definition
The gas in an MDI that provides pressure to expel product
Also serves as the dispersion medium (can occasionally even exhibit solvent properties) |
|
|
Term
| List roles of the solvent in a MDI |
|
Definition
-Bring active ingredient into solution
–Co-solvent for immiscible liquids
–Influence particle size
–Reduce vapor pressure |
|
|
Term
| Are droplet sizes out of a MDI all the same? |
|
Definition
| No, they are heterogenous and vary widely |
|
|
Term
| What kind of containers can an MDI be made of? |
|
Definition
Aluminum (most common)
Coated glass (not as safe)
PET (under development) |
|
|
Term
| How large is the typical MDI metered dose? |
|
Definition
|
|
Term
| What are the two propellant types? |
|
Definition
Chlorofluorocarbons (CFCs)
Hydrofluioroalkanes(HFAs) |
|
|
Term
| List disadvantages of CFSs |
|
Definition
Destroys ozone
Greenhouse gas
Expensive |
|
|
Term
|
Definition
Low toxicity
High stability
Good solvent |
|
|
Term
| List disadvantages of HFAs |
|
Definition
Poor solvent
Greenhouse gas
Expensive |
|
|
Term
|
Definition
Low toxicity
High stability
Non-ozone depleting |
|
|
Term
| Why did MDIs switch to HFAs instead of using CFCs? |
|
Definition
| Montreal Protocol: phase out CFCs by 2000, complete transition by 2005 |
|
|
Term
|
Definition
| Crystal growth- to be avoided in a drug in an aerosol formulation |
|
|
Term
| Do aerosol drugs always have to be soluble? |
|
Definition
| They can be soluble or insoluble, but no where in between |
|
|
Term
| Describe Baffles/Spacer Devices in MDIs |
|
Definition
A spacer in between inhaler and patient
-Allows solvent evaporation
-Loss of inertia
-Large particle sedimentation |
|
|
Term
| When were DPIs first introduced? |
|
Definition
| 1970s, in an attempt to phase out CFCs |
|
|
Term
|
Definition
-No propellant needed (eco-friendly)
-No coordination required
-Stability
-Dose |
|
|
Term
|
Definition
|
|
Term
| How is a powdered dose converted into an aerosol for inhalation in a DPI? |
|
Definition
The powdered dose needs to be fluidized
This is complex physics and involves particle size/attraction |
|
|
Term
| In generating an aerosol from powder, what prevents fluidization? How would you fix this? |
|
Definition
Inter-particulate forces between particles less than 5 microns
Why a carrier (ex lactose) of 40-60 microns is used |
|
|
Term
|
Definition
| Passive DPIs depend on the patient's inhalation to provide energy needed for dispersing a powder |
|
|
Term
| When would a passive DPI not be appropriate? |
|
Definition
| For pediatrics, elderly, or smokers since they can't inhale as strongly |
|
|
Term
|
Definition
They use an external source of energy to disperse powder, so it doesn't matter how good the patient's lungs are
Electric, pneumatic, and mechanical ones in development |
|
|
Term
| List the steps to make and QC a DPI |
|
Definition
1. Select excipients
2. Choose manufacturing method
3. Improve powder (de-aggregation, fluidization)
4. Device selection and calibration |
|
|
Term
| What is the most common respiratory dosage form excipients |
|
Definition
|
|
Term
| List the three drug classes that can treat asthma |
|
Definition
1. Beta-2 agonists
2. Glucocoricoids
3. Mast cell stabilizers |
|
|
Term
| List examples of beta-2 agonists for asthma |
|
Definition
Catecholamines - epinephrine, isoproterenol
Resorcinols - Terbutaline, fenoterol
Saligenins - Albuterol
Prodrugs – Bitolterol |
|
|
Term
| List four examples of glucocorticoids for asthma |
|
Definition
beclomethasone
triamcinolone
fluticasone
Budesonide |
|
|
Term
| List two examples of mast cell stabilizers for asthma |
|
Definition
| Cromolyn sodium, nedocromil |
|
|
Term
| List two drugs given by respiratory ROA for cystic fibrosis |
|
Definition
rhDNAse - cleaves leukocyte DNA
Tobramycin - Treat Pseudomonas aeruginosa infection |
|
|
Term
| List a drug given by respiratory ROA for emphysema |
|
Definition
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