EXAM 3 L4 Flashcards
Inhalation dosage forms
For local (asthma, COPD, lung infections) and systemic (diabetes) applications
Local application
High local concentration
Fast Action at the site if pulmonary diseases
Lower systemic side effects
Systemic application
Rapid absorption
Fewer drug-metabolizing enzymes
Inhaled fluticasone properties
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
Systemic app. of inhaled meds
-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)
Aerodynamic diameter (Dae)
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)
Extrathoracic region properties
Airways in head and neck
Upper and Lower bronchial region properties
-Upper - Trachea and bronchi (large ciliated thoracic airways)
-Lower - Bronchioles (small, ciliated thoracic airways)
Alveolar region
Nonciliated thoracic airways and airspaces
Particle deposition mechanisms
Diffusional Transport
Inertial Transport
Gravitational Transport
Inertial Transport
-(Impaction)
-Driven by momentum
-Increase with particle velocity, diameter, density
-Extrathoracic region
Diffusional Transport
Ultrafine particles (<0.1 nanometer)
Lung periphery (alveoli)
Tend to be exhaled without depositing
Alveolar region
Gravitational Transport
(Sedimentation)
Particles >0.1nanometer
Increase with diameter and density
Bronchial region; alveolar region
Factors determining particle sedimentation
-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)
Particle with a unit density vs low density particle
Different geometric diameters, SAME aerodynamic diameters
T/F: In pulmonary drug delivery system, particles with aerodynamic diameter >5 nm will normally deposit in upper airways due to inertial impaction
True
T/F: Particles with aerodynamic diameter 1-5 nm will mostly deposit in upper airways
False, lower airways
T/F: Particles with aerodynamic sizes < 1 nm may be exhaled
True
Challenges in pulmonary drug delivery are due to
Due to the defense mechanisms of the lung
Challenges in pulmonary drug delivery Upper (head) airways
-Filtering mechanisms in the nasal cavity trap and eliminate large particles (>10nm)
-Reflexes: sneezing and coughing
Challenges in pulmonary drug delivery conducting (lung) airways
-Mucociliary escalator
IgA (an antibody produced by plasma cells in the submucosa)
Challenges in pulmonary drug delivery in the alveoli
-Alveolar macrophages
-Immunologic mechanisms: T & B lymphocytes; IgG
Types of aerosols
-Liquid droplets
Pressurized metered-dose inhalers (pMDIs)
Nebulizers
-Dry particles
Dry powder inhalers (DPIs)
Propellant-driven (“pressurized”) metered-dose inhalers (pMDI):
-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
pMDI needs….
Good inhalation technique (for children spacer needed)
pMDI characteristics:
-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
Components of pMDI
-Drug
-Propellant
Chlorofluorocarbon (CFC)
Hydrofluoroalkanes (HFA)
-Cosolvent
Ethanol
-Surfactant
Sorbitan trioleate, oleic acid, lecithin
Nebulizers
-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
Jet Nebulizers
-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
New Nebulizer properties
-Smaller than traditional jet nebulizers
-Higher delivery efficiency
-Lower residues
-New types:
Vibration mesh nebulizer
Soft mist inhaler
Dry Powder Inhalers (DPI):
-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
DPI devices
-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
Single unit dose
Inhaler is smaller
Design is relatively simple
Multiple unit-dose
-Convenient for frequent use
-Inhaler is larger
-Design is relatively complex
Particle production forms
-Mechanical milling: applying mechanical forces to break coarse particles
-Jet milling: used in pharm. industry to produce inhalable drug particles
-Spray drying
Jet milling
-Jet milled particles are typically COHESIVE WITH HIGH SURFACE ENERGY and HIGH ELECTROSTATIC CHARGE
-Poor flowability and poor aerosolization
Spray drying
Drug is dissolved in a solvent, atomized into small droplets, and dried by hot airflow through solvent evaporation
Particle interaction types:
-Van Der Waals forces
-Electrostatic interactions (significant for some materials at dry conditions)
-Capillary forces (Significant for hygroscopic particles at high humidity)
-Mechanical Interlocking
Particle deposition is influenced by:
-Particle geometric diameter
-Density
-Morphology
-Surface energy
-Electrostatic charge
-Hygroscopicity
Carrier-based DPI formulations
-Carriers act as a filler for low-dose drugs
-Improve flowability
Aerosol performance depends on carriers properties:
-Particle geometric diameter
-Morphology
-Surface energy
-Electrostatic charge
-Drug to carrier ratio
-Addition of additives
