Podcast
Questions and Answers
How does the mucociliary clearance mechanism affect pulmonary drug delivery?
How does the mucociliary clearance mechanism affect pulmonary drug delivery?
- It enhances drug absorption by increasing the contact time between the drug and the alveolar epithelium.
- It promotes drug retention in the upper airways, reducing systemic exposure.
- It removes inhaled particles, potentially reducing the amount of drug reaching the target site. (correct)
- It facilitates uniform drug distribution throughout the respiratory tract.
What is a primary advantage of pulmonary drug delivery for systemic drug action compared to oral administration?
What is a primary advantage of pulmonary drug delivery for systemic drug action compared to oral administration?
- Avoidance of first-pass metabolism and enzymatic degradation. (correct)
- Increased drug metabolism due to higher enzyme activity in the lungs.
- Slower drug absorption leading to a prolonged therapeutic effect.
- More predictable and consistent drug absorption rates.
Which of the following is the definition of aerodynamic diameter?
Which of the following is the definition of aerodynamic diameter?
- The actual physical size of an irregular particle measured using microscopy.
- The diameter of a hypothetical sphere with a density of 1 g/cm³ having the same settling velocity as the particle in question. (correct)
- The average diameter of particles in an aerosol cloud, determined by laser diffraction.
- The diameter of a sphere with a density of 2 g/cm³ that settles at the same rate as the particle.
How does inertial impaction affect aerosol deposition in the respiratory tract?
How does inertial impaction affect aerosol deposition in the respiratory tract?
Which particle size range is generally considered optimal for alveolar deposition in pulmonary drug delivery?
Which particle size range is generally considered optimal for alveolar deposition in pulmonary drug delivery?
How does a broad particle size distribution (high Geometric Standard Deviation) affect pulmonary drug delivery?
How does a broad particle size distribution (high Geometric Standard Deviation) affect pulmonary drug delivery?
How does particle density influence aerosol deposition in the lungs?
How does particle density influence aerosol deposition in the lungs?
How does hygroscopicity affect the deposition of aerosol particles in the lungs?
How does hygroscopicity affect the deposition of aerosol particles in the lungs?
Which statement correctly describes the relationship between particle shape and aerosol deposition?
Which statement correctly describes the relationship between particle shape and aerosol deposition?
If a drug is administered using a nebulizer and the patient exhales during the treatment, what is a potential consequence?
If a drug is administered using a nebulizer and the patient exhales during the treatment, what is a potential consequence?
Which of the following is an advantage of using a nebulizer for pulmonary drug delivery?
Which of the following is an advantage of using a nebulizer for pulmonary drug delivery?
What is a key limitation of ultrasonic nebulizers compared to air-jet nebulizers?
What is a key limitation of ultrasonic nebulizers compared to air-jet nebulizers?
What property is required in a formulation for inhalation administered via nebulizer?
What property is required in a formulation for inhalation administered via nebulizer?
What is a common type of drug administered via pMDIs?
What is a common type of drug administered via pMDIs?
What is an advantage of metered-dose inhalers (MDIs) compared to nebulizers?
What is an advantage of metered-dose inhalers (MDIs) compared to nebulizers?
Auxiliary systems are used in conjunction with pMDIs. How do spacer devices enhance aerosol deposition in the lungs?
Auxiliary systems are used in conjunction with pMDIs. How do spacer devices enhance aerosol deposition in the lungs?
How does valve design in a pMDI affect aerosol characteristics?
How does valve design in a pMDI affect aerosol characteristics?
What is the role of the propellant in a pMDI formulation?
What is the role of the propellant in a pMDI formulation?
What is a limitation of hydrofluoroalkanes (HFAs) used as propellants in pMDIs?
What is a limitation of hydrofluoroalkanes (HFAs) used as propellants in pMDIs?
Which factor is most crucial for achieving optimal drug delivery with dry powder inhalers (DPIs)?
Which factor is most crucial for achieving optimal drug delivery with dry powder inhalers (DPIs)?
What is an advantage of DPIs compared to pMDIs for pulmonary drug delivery?
What is an advantage of DPIs compared to pMDIs for pulmonary drug delivery?
What is the process of converting a powder dose into an aerosol called?
What is the process of converting a powder dose into an aerosol called?
What is the role of carrier particles, such as lactose, in DPI formulations?
What is the role of carrier particles, such as lactose, in DPI formulations?
Inhaling at a maximum rate into a DPI is an important step for administration. Why is this necessary?
Inhaling at a maximum rate into a DPI is an important step for administration. Why is this necessary?
How do inter-particulate forces affect dry powder inhalation?
How do inter-particulate forces affect dry powder inhalation?
Which of the following describes a "passive" DPI?
Which of the following describes a "passive" DPI?
What is geometric diameter by mass in reference to particle size determination?
What is geometric diameter by mass in reference to particle size determination?
How does porosity of an aerosolized powder affect its performance in pulmonary delivery?
How does porosity of an aerosolized powder affect its performance in pulmonary delivery?
What is the definition of volume diameter in particle size determination?
What is the definition of volume diameter in particle size determination?
Besides drug delivery for asthma and COPD, what is another application of pulmonary delivery via DPIs?
Besides drug delivery for asthma and COPD, what is another application of pulmonary delivery via DPIs?
What is a consideration in the preparation of a DPI formulation?
What is a consideration in the preparation of a DPI formulation?
What is the purpose of using experimental approaches for formulation ingredients like PLGA or Chitosan?
What is the purpose of using experimental approaches for formulation ingredients like PLGA or Chitosan?
Which region of the respiratory tract is characterized by the presence of ciliated cells that contribute to the mucociliary clearance mechanism?
Which region of the respiratory tract is characterized by the presence of ciliated cells that contribute to the mucociliary clearance mechanism?
What is a key challenge associated with pulmonary drug delivery for systemic action?
What is a key challenge associated with pulmonary drug delivery for systemic action?
How does the anatomical structure of the nasal cavity primarily influence aerosol deposition?
How does the anatomical structure of the nasal cavity primarily influence aerosol deposition?
How does increased airflow velocity in the upper respiratory tract affect aerosol deposition?
How does increased airflow velocity in the upper respiratory tract affect aerosol deposition?
Why is a narrow particle size distribution important for pulmonary drug delivery?
Why is a narrow particle size distribution important for pulmonary drug delivery?
How would increasing the density of an aerosol particle affect its deposition via inertial impaction?
How would increasing the density of an aerosol particle affect its deposition via inertial impaction?
What is a consequence of high hygroscopicity of aerosol particles in pulmonary drug delivery?
What is a consequence of high hygroscopicity of aerosol particles in pulmonary drug delivery?
How does a highly irregular particle shape affect aerosol deposition in the lungs?
How does a highly irregular particle shape affect aerosol deposition in the lungs?
In the operation of a nebulizer, what is the function of the baffle?
In the operation of a nebulizer, what is the function of the baffle?
Which of the following is a limitation of air-jet nebulizers compared to ultrasonic nebulizers?
Which of the following is a limitation of air-jet nebulizers compared to ultrasonic nebulizers?
Why is sterility a critical requirement for solutions used in nebulizers?
Why is sterility a critical requirement for solutions used in nebulizers?
Which drug is commonly administered via pMDIs to quickly relieve acute asthma symptoms?
Which drug is commonly administered via pMDIs to quickly relieve acute asthma symptoms?
What is a disadvantage of metered-dose inhalers (MDIs) compared to dry powder inhalers (DPIs)?
What is a disadvantage of metered-dose inhalers (MDIs) compared to dry powder inhalers (DPIs)?
What is the primary purpose of a holding chamber or spacer in pMDI therapy?
What is the primary purpose of a holding chamber or spacer in pMDI therapy?
How does the metering valve in a pMDI contribute to the delivery of a consistent dose?
How does the metering valve in a pMDI contribute to the delivery of a consistent dose?
What is the purpose of the propellant in a pMDI?
What is the purpose of the propellant in a pMDI?
What is a disadvantage of using hydrofluoroalkanes (HFAs) as propellants in pMDIs compared to older chlorofluorocarbons (CFCs)?
What is a disadvantage of using hydrofluoroalkanes (HFAs) as propellants in pMDIs compared to older chlorofluorocarbons (CFCs)?
What patient-related factor is most critical for optimizing drug delivery with DPIs?
What patient-related factor is most critical for optimizing drug delivery with DPIs?
How does the required inspiratory flow rate of DPIs affect their suitability for different patient populations?
How does the required inspiratory flow rate of DPIs affect their suitability for different patient populations?
What is the primary mechanism by which a dry powder is dispersed into an aerosol within a DPI?
What is the primary mechanism by which a dry powder is dispersed into an aerosol within a DPI?
What is the purpose of lactose in a DPI formulation?
What is the purpose of lactose in a DPI formulation?
For a passive DPI, what is the significance of a patient's ability to inhale at a high flow rate?
For a passive DPI, what is the significance of a patient's ability to inhale at a high flow rate?
How do strong inter-particulate forces primarily affect the performance of DPIs?
How do strong inter-particulate forces primarily affect the performance of DPIs?
What is the energy source for aerosol generation in a 'passive' DPI?
What is the energy source for aerosol generation in a 'passive' DPI?
What does the Kelvin equation describe in the context of powder characterization?
What does the Kelvin equation describe in the context of powder characterization?
How does porosity affect the performance of an aerosolized powder in pulmonary delivery?
How does porosity affect the performance of an aerosolized powder in pulmonary delivery?
What property is most relevant to systemic drug delivery when characterizing an aerosolized powder via pulmonary route?
What property is most relevant to systemic drug delivery when characterizing an aerosolized powder via pulmonary route?
Besides local treatment of respiratory diseases, what other therapeutic area is being explored for pulmonary delivery using DPIs?
Besides local treatment of respiratory diseases, what other therapeutic area is being explored for pulmonary delivery using DPIs?
In the formulation of DPIs, why is controlling the moisture content of the powder blend crucial?
In the formulation of DPIs, why is controlling the moisture content of the powder blend crucial?
What is a primary reason for using biodegradable polymers like PLGA or chitosan in experimental pulmonary delivery formulations?
What is a primary reason for using biodegradable polymers like PLGA or chitosan in experimental pulmonary delivery formulations?
Which anatomical region of the respiratory system contains the terminal bronchioles?
Which anatomical region of the respiratory system contains the terminal bronchioles?
What is one of the primary advantages of pulmonary delivery for drugs intended to have a local effect?
What is one of the primary advantages of pulmonary delivery for drugs intended to have a local effect?
Which aerosol deposition mechanism is primarily influenced by particle size between 5 and 10 μm?
Which aerosol deposition mechanism is primarily influenced by particle size between 5 and 10 μm?
What is a major limitation of pulmonary drug delivery?
What is a major limitation of pulmonary drug delivery?
What does the diagram of an AIR JET Nebulizer indicate about how particles impact efficacy?
What does the diagram of an AIR JET Nebulizer indicate about how particles impact efficacy?
How does the design of the actuator in a pMDI impact the aerosol generated?
How does the design of the actuator in a pMDI impact the aerosol generated?
Considering the anatomical variations in the respiratory tract, how does the presence of alveolar macrophages influence pulmonary drug delivery strategies targeting the lower respiratory tract?
Considering the anatomical variations in the respiratory tract, how does the presence of alveolar macrophages influence pulmonary drug delivery strategies targeting the lower respiratory tract?
How does the aerodynamic diameter of an aerosol particle directly relate to its behavior in an air stream during pulmonary drug delivery?
How does the aerodynamic diameter of an aerosol particle directly relate to its behavior in an air stream during pulmonary drug delivery?
What is a critical consideration for optimizing the aerosolization of drug suspensions using nebulizers, as opposed to drug solutions?
What is a critical consideration for optimizing the aerosolization of drug suspensions using nebulizers, as opposed to drug solutions?
How does the use of auxiliary systems like spacer devices with pressurized metered-dose inhalers (pMDIs) impact drug delivery to the lungs?
How does the use of auxiliary systems like spacer devices with pressurized metered-dose inhalers (pMDIs) impact drug delivery to the lungs?
In the context of dry powder inhalers (DPIs), what is the primary role of a carrier particle, such as lactose, in the drug formulation?
In the context of dry powder inhalers (DPIs), what is the primary role of a carrier particle, such as lactose, in the drug formulation?
What is the primary reason for the lungs being 'inefficient' in pulmonary drug delivery?
What is the primary reason for the lungs being 'inefficient' in pulmonary drug delivery?
In the context of aerosol deposition, how does particle interception primarily occur?
In the context of aerosol deposition, how does particle interception primarily occur?
How do the rapid directional changes in the upper respiratory tract influence aerosol deposition?
How do the rapid directional changes in the upper respiratory tract influence aerosol deposition?
Why is the optimization of droplet size particularly important when using nebulizers with suspensions compared to solutions?
Why is the optimization of droplet size particularly important when using nebulizers with suspensions compared to solutions?
What is the significance of geometric standard deviation (GSD) in pulmonary drug delivery?
What is the significance of geometric standard deviation (GSD) in pulmonary drug delivery?
Why might small particles be less effective than larger particles for pulmonary drug delivery?
Why might small particles be less effective than larger particles for pulmonary drug delivery?
What role does density play in affecting aerosol deposition in the lungs?
What role does density play in affecting aerosol deposition in the lungs?
How does a particle's shape primarily influence its deposition pattern in the respiratory tract?
How does a particle's shape primarily influence its deposition pattern in the respiratory tract?
How does the solubility of a dry powder for inhalation relate to its performance?
How does the solubility of a dry powder for inhalation relate to its performance?
What is a primary factor determining droplet size in a nebulizer?
What is a primary factor determining droplet size in a nebulizer?
Why is sterility an important consideration in nebulizer formulations?
Why is sterility an important consideration in nebulizer formulations?
What is the purpose of a baffle in an air-jet nebulizer?
What is the purpose of a baffle in an air-jet nebulizer?
Considering the mechanism of aerosol generation in pMDIs, what primarily determines the size of emitted particles?
Considering the mechanism of aerosol generation in pMDIs, what primarily determines the size of emitted particles?
Auxiliary systems like spacer devices are used with pMDIs to optimize drug delivery. How?
Auxiliary systems like spacer devices are used with pMDIs to optimize drug delivery. How?
What is the role of solvents in pMDI formulations?
What is the role of solvents in pMDI formulations?
What is an advantage of DPIs compared to pMDIs?
What is an advantage of DPIs compared to pMDIs?
What is a key factor that the patient must learn to optimize effective drug delivery from a DPI?
What is a key factor that the patient must learn to optimize effective drug delivery from a DPI?
What is the primary purpose of fluidizing a DPI powder?
What is the primary purpose of fluidizing a DPI powder?
What role do carrier particles play in DPI formulations?
What role do carrier particles play in DPI formulations?
In a passive DPI, what does powder dispersion rely on?
In a passive DPI, what does powder dispersion rely on?
What does the Kelvin equation help determine in the context of aerosolized powders?
What does the Kelvin equation help determine in the context of aerosolized powders?
Why is it essential to control the moisture content of DPI formulations?
Why is it essential to control the moisture content of DPI formulations?
The terminal bronchioles are closest to which location?
The terminal bronchioles are closest to which location?
What particle size would primarily deposit in the turbulent change from NASAL to PHARYNGEAL region?
What particle size would primarily deposit in the turbulent change from NASAL to PHARYNGEAL region?
A nebulizer delivers liquid formulations, but does not:
A nebulizer delivers liquid formulations, but does not:
A burst of Hydrofluoroalkanes into the face or eyes from a pMDI is:
A burst of Hydrofluoroalkanes into the face or eyes from a pMDI is:
What is the rationale for using aerosol inhalation locally for ailments such as COPD or Asthma?
What is the rationale for using aerosol inhalation locally for ailments such as COPD or Asthma?
The components of pMDI do NOT include:
The components of pMDI do NOT include:
Why is tobramycin delivered to the lungs via nebulization?
Why is tobramycin delivered to the lungs via nebulization?
If greater levels of localized aerosol deposition are sought in a treatment plan, which of these methods for delivery would be best?
If greater levels of localized aerosol deposition are sought in a treatment plan, which of these methods for delivery would be best?
If a formulation engineer is concerned about the shape of the aerosol under development, what would be the concern?
If a formulation engineer is concerned about the shape of the aerosol under development, what would be the concern?
What are solutions for injection used to treat when administering to the lungs via nebulizer?
What are solutions for injection used to treat when administering to the lungs via nebulizer?
Match the disease state to how it's administered: Asthma/COPD
Match the disease state to how it's administered: Asthma/COPD
Why were chlorofluorocarbons (CFCs) phased out as propellants from pMDIs?
Why were chlorofluorocarbons (CFCs) phased out as propellants from pMDIs?
A key advantage of dry powder inhalers does NOT include:
A key advantage of dry powder inhalers does NOT include:
Powder blends of DPIs can be distinguished BEST as:
Powder blends of DPIs can be distinguished BEST as:
Why would PLGA or Chitosan be considered for experimental approaches to treat lungs?
Why would PLGA or Chitosan be considered for experimental approaches to treat lungs?
How does the variation in cell composition along the respiratory tract affect drug absorption following pulmonary delivery?
How does the variation in cell composition along the respiratory tract affect drug absorption following pulmonary delivery?
What is a key challenge associated with pulmonary drug delivery regarding consistent dosing?
What is a key challenge associated with pulmonary drug delivery regarding consistent dosing?
Why is aerodynamic diameter crucial in the context of aerosol deposition?
Why is aerodynamic diameter crucial in the context of aerosol deposition?
Which factor primarily governs the mechanism of aerosol deposition in the alveolar region?
Which factor primarily governs the mechanism of aerosol deposition in the alveolar region?
How does the selection of a specific aerosol-generating device impact the efficacy of pulmonary drug delivery?
How does the selection of a specific aerosol-generating device impact the efficacy of pulmonary drug delivery?
What is the most important factor to consider in optimizing the physicochemical characteristics of an emitted dose for pulmonary delivery?
What is the most important factor to consider in optimizing the physicochemical characteristics of an emitted dose for pulmonary delivery?
What is an advantage of pulmonary drug delivery that is particularly beneficial for systemically acting drugs?
What is an advantage of pulmonary drug delivery that is particularly beneficial for systemically acting drugs?
A patient with a severe cough has difficulty using a dry powder inhaler. How will deposition be affected?
A patient with a severe cough has difficulty using a dry powder inhaler. How will deposition be affected?
How does the use of tobramycin in a nebulizer benefit patients with cystic fibrosis?
How does the use of tobramycin in a nebulizer benefit patients with cystic fibrosis?
What is a major disadvantage of nebulizers?
What is a major disadvantage of nebulizers?
What aspect of an air-jet nebulizer contributes significantly to the formation of smaller aerosol droplets?
What aspect of an air-jet nebulizer contributes significantly to the formation of smaller aerosol droplets?
What is the primary reason for using solutions for injection as starting materials in nebulizer formulations?
What is the primary reason for using solutions for injection as starting materials in nebulizer formulations?
How does the addition of a spacer device improve drug delivery with a pMDI?
How does the addition of a spacer device improve drug delivery with a pMDI?
In addition to the active drug, what are the other primary components in a pMDI formulation that contribute to aerosolization?
In addition to the active drug, what are the other primary components in a pMDI formulation that contribute to aerosolization?
What is a characteristic of a formulation for a passive dry powder inhaler (DPI)?
What is a characteristic of a formulation for a passive dry powder inhaler (DPI)?
What is the purpose of the powder fluidization process in DPIs?
What is the purpose of the powder fluidization process in DPIs?
How do inter-particulate forces affect the performance of dry powder inhalers?
How do inter-particulate forces affect the performance of dry powder inhalers?
Aside from the active drug, what other type of excipient is commonly found in DPI formulations?
Aside from the active drug, what other type of excipient is commonly found in DPI formulations?
What key principle does the Kelvin equation describe in the context of aerosolized powders?
What key principle does the Kelvin equation describe in the context of aerosolized powders?
Which property of an aerosolized powder critically affects both local and systemic drug delivery?
Which property of an aerosolized powder critically affects both local and systemic drug delivery?
Pulmonary delivery via DPIs is being explored for the treatment of which disease state, aside from Asthma or COPD?
Pulmonary delivery via DPIs is being explored for the treatment of which disease state, aside from Asthma or COPD?
Why is controlling moisture content crucial for optimizing DPI formulations?
Why is controlling moisture content crucial for optimizing DPI formulations?
What region is closest to the terminal bronchioles?
What region is closest to the terminal bronchioles?
What occurs if the burst from a pMDI contacts the eye?
What occurs if the burst from a pMDI contacts the eye?
What rationale supports aerosol inhalation locally for ailments such as COPD or Asthma?
What rationale supports aerosol inhalation locally for ailments such as COPD or Asthma?
What concern might a formulation engineer have regarding shape of an aerosol under development?
What concern might a formulation engineer have regarding shape of an aerosol under development?
Match the disease state to how it's administered: Cystic Fibrosis
Match the disease state to how it's administered: Cystic Fibrosis
How may the volume of solution affect droplet size using a nebulizer?
How may the volume of solution affect droplet size using a nebulizer?
What is the primary rationale behind administering rhDNAse via nebulization to individuals with cystic fibrosis?
What is the primary rationale behind administering rhDNAse via nebulization to individuals with cystic fibrosis?
Inhaled tobramycin solutions do NOT include.
Inhaled tobramycin solutions do NOT include.
In the process of aerosol generation in air jet nebulizers, where do bigger droplets hit?
In the process of aerosol generation in air jet nebulizers, where do bigger droplets hit?
How might a formulation scientist adjust the characteristics of a drug when using an Air Jet nebulizer?
How might a formulation scientist adjust the characteristics of a drug when using an Air Jet nebulizer?
In the context of aerosol deposition, what scenario would most favor drug delivery to the alveolar region?
In the context of aerosol deposition, what scenario would most favor drug delivery to the alveolar region?
How does the use of lactose as a carrier in DPI formulations affect the delivery of a drug to the lower respiratory tract?
How does the use of lactose as a carrier in DPI formulations affect the delivery of a drug to the lower respiratory tract?
If a dry powder formulation for inhalation has a high degree of porosity, how would this characteristic influence its aerosolization and deposition?
If a dry powder formulation for inhalation has a high degree of porosity, how would this characteristic influence its aerosolization and deposition?
A pharmaceutical company is reformulating a pMDI product to replace chlorofluorocarbons (CFCs). What considerations might rise in this process when switching to hydrofluoroalkanes (HFAs)?
A pharmaceutical company is reformulating a pMDI product to replace chlorofluorocarbons (CFCs). What considerations might rise in this process when switching to hydrofluoroalkanes (HFAs)?
Flashcards
Respiratory System
Respiratory System
Anatomical division including the trachea, primary bronchus, primary bronchiole, secondary bronchiole, terminal bronchiole, respiratory bronchiole, alveolar duct and alveoli.
Aerodynamic Diameter
Aerodynamic Diameter
The diameter of a hypothetical sphere of density = 1 g/cm³ having the same terminal settling velocity in calm air as the particle in question, regardless of its geometric size, shape and true density.
Aerosol
Aerosol
A dispersion of particles or droplets suspended in a gas or vapor.
Aerosol Deposition by Impaction
Aerosol Deposition by Impaction
A method for depositing particles > 5 μm, based on higher mass and velocity striking airway bifurcations.
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Aerosol Deposition by Electrostatic Attraction
Aerosol Deposition by Electrostatic Attraction
A method for depositing particles, where electrostatic forces attract charged particles with high efficiency.
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Aerosol Deposition by Gravitational settling
Aerosol Deposition by Gravitational settling
A method for depositing particles < 5 μm via gravity settling in the airways.
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Aerosol Deposition by Brownian diffusion
Aerosol Deposition by Brownian diffusion
A method for depositing particles < 1 μm, due to random collision of molecules.
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Nebulizer
Nebulizer
A device using compressed gas to aerosolize liquid formulations for inhalation, commonly used in hospitals.
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Air-Jet Nebulizers
Air-Jet Nebulizers
Nebulizers that work via flow of compressed gas through a liquid.
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Ultrasonic Nebulizers
Ultrasonic Nebulizers
Nebulizers that utilize vibrating crystal to turn liquids into aerosol mists.
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Nebulizer Advantage
Nebulizer Advantage
Advantage of nebulizers in which you don't need coordination from people with the device.
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pMDI (Pressurized Metered Dose Inhaler)
pMDI (Pressurized Metered Dose Inhaler)
Device that delivers fixed, aerosolized doses of medication in a propellant.
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pMDI Propellants
pMDI Propellants
Ingredient required in pMDIs, providing force to expel product, act as a dispersion medium, and exhibit solvent properties.
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pMDI Solvents
pMDI Solvents
Ingredient found in pMDIs; dissolves the active ingredient
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Dry Powder Inhalers (DPIs)
Dry Powder Inhalers (DPIs)
Devices delivering solid drug powder to the lungs, requiring patient's inhalation for dispersion.
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Passive DPIs
Passive DPIs
Depend on the patient's inhalation to provide the energy needed to disperse the powder.
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Carrier Particles in DPI
Carrier Particles in DPI
Used in DPI formulations. Helps in powder flow, uniform mixing, and aerosolization
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Porosity
Porosity
Measurement of void spaces in powder.
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Aerodynamic Diameter's impact
Aerodynamic Diameter's impact
Describes how well a particle or droplet travels ('flies') in an air stream.
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Pulmonary Delivery Limitations
Pulmonary Delivery Limitations
The lungs are designed to prevent inhalation of exogenous compounds/particulates; some devices deliver only ~10% of dose to lungs.
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Rationale for Inhalation Aerosols
Rationale for Inhalation Aerosols
Localized delivery to the site of action, avoids systemic effects, rapid onset and are acceptable.
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Factors Influencing Deposition
Factors Influencing Deposition
Particle size and its distribution have the most significant role in aerosol deposition.
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Geometric Standard Deviation (GSD)
Geometric Standard Deviation (GSD)
Describes how broad the distribution of particle sizes are around a population mean.
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Density's effect on deposition
Density's effect on deposition
Density of the particle or droplet that contributes to inertia.
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Particle Shape & Deposition
Particle Shape & Deposition
Serious deviation from sphericity affects deposition.
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Solubility/Hygroscopicity
Solubility/Hygroscopicity
Influence deposition in the lungs due to high humidity.
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Metered Dose Inhalers
Metered Dose Inhalers
Metered dose inhalers contain a pressurized formulation that is aerosolized through an atomization nozzle.
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Advantages of MDIs
Advantages of MDIs
Portable, easy to use, stable, and tamper-proof.
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Factors Affecting Nebulizer Doses
Factors Affecting Nebulizer Doses
Dependent on droplet size, volume, surface tension, and device.
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Mechanism of pMDI
Mechanism of pMDI
The canister of a pMDI is pressed against the actuator, which opens the metering valve and releases the drug.
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Formulation Ingredients of DPI
Formulation Ingredients of DPI
Consists of powder blends (drug and carrier) and engineered particles.
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Fluidized Powder in DPIs
Fluidized Powder in DPIs
The powder must be fluidized before being delivered to the patient during inhalation.
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Factors Affecting DPI Performance
Factors Affecting DPI Performance
Physics of powder fluidization dependent on particle sizes and attractive forces
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Learning Objectives of Pulmonary Delivery
- Describe regional variations in respiratory tract anatomy, cell composition, and clearance mechanisms and their influence on pulmonary drug delivery.
- Explain the advantages, limitations, and challenges of pulmonary drug and vaccine administration.
- Define AERODYNAMIC DIAMETER and its impact on aerosol deposition mechanisms.
- Discuss different AEROSOL DEPOSITION MECHANISMS and influencing factors.
- Recognize the relevance of aerosol generation devices for pulmonary delivery efficacy and efficiency.
- Explain AEROSOL GENERATION mechanisms for devices used in pulmonary delivery.
- List and explain the ingredients of pulmonary delivery formulations and their roles.
- Identify and explain factors affecting physicochemical characteristics of the emitted dose and how to optimize treatments for maximum efficacy and efficiency.
- Describe the application of pulmonary delivery for local and systemic effects.
Outline of Pulmonary Delivery
- Anatomy and Physiology of the respiratory system.
- Discuss the advantages, limitations, and challenges of pulmonary delivery.
- Mechanisms of aerosol deposition.
- Devices and formulations for pulmonary delivery.
- Factors influencing performance and efficiency of treatments.
- Highlight delivery treatments with Nebulizers, Pressurized Metered Dose Inhalers (pMDI), and Dry Powder Inhalers (DPIs).
The Respiratory System
- Consists of the:
- Nasal Cavity
- Oral Cavity
- Larynx
- Trachea
- Bronchi
- Lungs
- Alveoli
- Bronchioles
- Alveolar Ducts
Aerosol Deposition and Air Velocity
- Nasopharyngeal region retains particles of aerodynamic size 10-30 μm through inertial impaction, at the highest air velocity.
- Bronchiolar region retains 5-10 μm aerodynamic diameter through sedimentation, at a moderate air velocity.
- Alveolar region retains particles of 1-5 μm diameter through diffusion, at the lowest air velocity.
Blood, Lymph Nodes, and Airways
- Drug in the nasal passages at >10μm enters the GI tract.
- Mucociliary clearance in the TB Airways can be cleared from the blood.
- TB Airways contain 5-10 μm.
- Alveoli and the lung tissue in the Pulmonary Parenchyma contains 1-5 μm.
- Macrophages and dendritic cells interact with the Lymph Nodes.
- Blood enters the blood stream
Relative Epithelial Cell Size and Surface Fluid Thickness
- This will vary with the Bronchioles, Bronchus and Alveoli in different regions of the lung
Aerosol Definition
- It is a dispersion of particles or droplets that are suspended in a gas or vapor.
Rationale of Inhalation Aerosols
- It offers locals and an immediate site of action.
- Treats Asthma and COPD.
- Avoids systemic effects using corticosteroids.
- Rapid onset via Beta-adrenergic agonists in acute Asthma cases.
- Has high acceptability compared to injections.
- Used for delivering systemically acting drugs.
- Large surface area (120-160m², about the size of a tennis court).
- There is no degradation by the stomach or enzymes.
- Avoids first-pass metabolisim in liver.
Limitations of Aerosols
- Lungs are inherently designed to prevent inhaling particulates.
- Only approximately 10% of the dose reaches the lungs via some devices.
- May cause Oropharyngeal irritation, and altered taste.
Aerodynamic Diameter Definition
- It is the diameter of a sphere with a density of 1 g/cm³ and the same settling velocity as the particle in question. For particles with various sizes, shapes, and true densities.
- Aerodynamic diameter influences how a droplet or particle flies in the air.
Aerosol Deposition Mechanisms
- Interception
- Electrostatic attraction
- Impaction for particles that are > 5 μm
- Gravitational settling/sedimentation
- Brownian diffusion for particles that are < 5 μm
Factors Influencing Aerosol Deposition: Particle Size and Distribution
- Plays the most significant role in deposition.
- A broad particle size distribution means there are fewer small particles and a larger amount of bigger particles.
- A Geometric Standard Deviation (GSD) that measures <2 is preferered.
Consequences if GSD > 2
- Effective inhaled dose in the lungs is reduced.
- Results in a loss of drug in the mouth and larger airways.
Factors Influencing Aerosol Deposition: Particle Size
- A collective number of very small particles performs similar to an amount of individual, bigger particles.
- An aerosol droplet is mostly solvent by volume, so it will not carry the same weight as a solid particle.
Further Factors Influencing Deposition: Density
- Particle and droplet density contribute to inertia.
- Physically larger particles can be aerodynamically smaller.
Further Factors Influencing Deposition: Shape of particles
- Deviation from spherical particles effects deposition.
- The dae value remains the same in the air stream.
Further Factors Influencing Deposition: Solubility/Hygroscopicity
- High humidity in the lungs influences deposition.
Recognizing Aerosol Delivery Significance
- Devices are important for generating AEROSOL for pulmonary delivery.
- Device choice influences the efficacy and efficiency of the treatment.
Devices for Pulmonary Drug Delivery
- Various conventional devices are used:
- Metered Dose Inhaler (MDI)
- Nebulizer
- Dry Powder Inhaler (DPI)
Compounds via Nebulization
- Cystic Fibrosis treatment uses:
- rhDNAse to cleave leukocyte DNA.
- Tobramycin to treat Pseudomonas aeruginosa.
- Emphysema treatments include:
- alpha₁-antitrypsin.
Nebulizers
- The oldest type of aerosol generating device.
- Often used for pediatric, geriatric, and hospital treatments.
- It can be classified based on its mechanism of aerosol production:
- Air-jet
- Ultrasonic
Nebulizers: Advantages
- These offer long treatment times.
- There are a variety of Aqueous solutions.
- These are easy to manufacture.
- Offers no environmental concerns.
- Good for biotech compounds.
- Does not depend on patient inspiratory force.
Nebulizers: Disadvantages
- Bulky/Not portable.
- Expensive.
- Poorly optimized.
- Leads to devices designed independently of a drug's properties.
- Experiences Wastage, as the drug is delivered when patients exhale.
- Can experience Contamination problems.
Air Jet Nebulizer Mechanisms
- Compressed air enters the nebulizer through a designated channel.
- The solution is present in the side channels.
- Air and solution combine quickly forming liquid droplets.
- Larger droplets hit the impinger.
- Smaller droplets form a liquid aerosol, exiting the device through tubing to the mask.
Physicochemical Characteristics of Nebulizers
- Droplet size depends on the volume of the solution, surface tension, density and viscosity, and nebulizer make/model.
- Needs to be optimized per drug, and each concentration.
- Additional optimization is needed when using solutions.
Ultrasonic Nebulizers
- Limitations of ultrasonic nebulizers can be degraded by heat.
- Sterility is required due to the piezoelectric transducer.
- Can make smaller droplets, but is less sufficient.
TOBI Formulation for Nebulizers
- TOBI was the initial formulation developed for nebulization.
- Solutions for injection, are typically used for nebulization.
- Antibiotic solutions had variable results due to the adverse events.
- Most antibiotic solutions have a non-irritating pH and osmolality.
Nebulizer Formulation
- A solution should be sterile and non-pyrogenic.
- Anti-infective solutions should be:
- Chemically stable.
- Free of preservatives and other toxic material.
- Have a non-irritating pH of 4.5-8.7.
- Osmolality of 150-550 mOsm/kg with the chloride ion concentration between 31-300 mM.
- Enhanced patient solutions should be tasteless or pleasant.
TOBI vs Inhaled Tobramycin
- TOBI is a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution, which uses either a compressed air or reusable jet nebulizer to deliver.
- It contains 300 mg Tobramycin and 11.25 mg of sodium chloride, it has a pH of 6.0, with all ingredients approved by USP.
- There are no preservatives.
- Tobramycin injection, USP, is a sterile colorless aqueous solution that delivers parentirally. It contains tobramycin sulfate, Phenol with 5 mg of preservatives and sodium metabisulfite with 3.2mg of multiple doses.It has a pH value ranging from 3.0 to 6.5.
Pressurized Metered Dose Inhalers (pMDI) Compounds
- Treats Asthma/ COPD
- Beta2-adrenergic agonists
- Glucocorticoids
- Mast cell stabilizer
Metered Dose Inhalers (MDI or pMDI)
- A pressurized formulation that produces a measured dose of Aerosolized drug that is inhaled by the patient via an atomization nozzle.
Advantages of pMDIs
- Portable.
- Perceived easy to use.
- Stable.
- Protect from light, oxygen, and water, and is tamper proof.
Disadvantages of pMDIs
- Expensive.
- Prone to incorrect use.
- May be or may cause Pressurized contents to be unsafe.
Components of a pMDI
- Canister.
- Valve.
- Actuator.
- Formulation ingredients:
- Propellants
- Solvents
- Active ingredients/other additives
Containers/Canisters for pMDIs
- Aluminum.
- Glass with a coating.
Valves
- Metered at 25 to 100 ul
- Continuous
Actuators Function
- Allows the release and the direct delivery of aerosols.
Auxiliary Systems
- Baffles.
- Spacer Devices with designs to reduce:
- Evaporation
- Loss of inertia
- Large particle sedimentation
Mechanism of Aerosol Generation pMDI
- Based on the formulation, valve, actuator, and propellant.
Further Mechanism of Aerosol Generation pMDI
- A canister is pressed against the actuator, causing the actuator seat to move the nozzle in the metering valve.
- With a second actuation, the drug fills the chamber in the valve.
- Actuation is used to release the aerosol through the mouthpiece.
- A spacer is effective by trapping residue for larger droplets.
Formulation Ingredients of a MDI
- Propellants provide pressure to expel the product.
- act as a dispersion medium.
- and exhibit solvent properties.
- Solvents bring:
- The active ingredient into solution.
- Can be a co-solvent for immiscible liquids.
- Influence particle size reduction of vapor pressure.
- Contains Active Ingredient in other additives.
Banned Propellants
- Where banned because of the effect they had on the Ozone Layer.
Types of Propellants
-
Chlorofluorocarbons (CFCs)
- have low toxicity
- High stability
- Good solvents
- CFCs destroy O3 (ODP)
-
Hydrofluoroalkanes (HFAs) : With less Global warming potential by six times (Low toxicity, High Stability, Non O3 depleting , Poor Solvents)
Factors That Influence Performance of MDIs
- Drug solubility.
- Vapor Pressure.
- Surface Tension.
- Solubility of O2/Hygroscopicity.
- Density.
Dry Powder Inhalers (DPI)
- Has no propellants.
- Has ease of use
- It Offers stability advantages for many drugs, especially biotech compounds, and for small or large doses.
Common DPI Products
- Turbuhaler
- (budesonide; budesonide/formoterol)
- Handihaler
- (tiotropium)
- Cyclohaler
- (Aerolizer/Formoterol)
- Diskus
- (Salmeterol/Fluticasone)
Advantages of DPI
- Convenient and Portable
- Delivers drugs higher by the nebulizers and Easier to use
- Less hand required for coordination
- More stable
- Tamper proof
DPI Compounds
- Treats Asthma and COPD
- Treats Insulin and Diabetes
- Combats Antibiotics
Disadvantages if DPI
- Dependant heavilly to formulation
- Air strength from the patients matters
- It is recommended to not be used for Children
General Facts about DPI
- The Inhaler depends on the patients to distribute the powder which provides energy.
- Maximizes for inhaler to perform properly
- The airflow determines the dose which is not for children or elderly people
The Main Parts of DPIs
- Powder Reservior
- Capsule (Spinhaler or Arelizer) Powder foil Blister
- The Mechanism of powder release and fludization.
- Rotating impeller in Spinhaier.
- Pircing pins or Capsul. Foil Sprocket with chamber.
- The final part is the Mouth Peice
Mechanism of aerosol generation: DPI
- The process involves transferring powder to the patient's airflow during inhalation. However static and airflow is required with the carrier and stripped drug based on particle size.
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