Lecture 4: Dry Powder Inhaler Flashcards by Brooke Thornburg

Inhalation dosage forms

-local and systemic

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Local application of inhalation dosage forms

-high local concentration
-fast action
-lower systemic side effects
-asthma, COPD, lung infection

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systemic application of inhalation dosage form

-rapid absorption
-fewer drug-metabolizing enzymes

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fluticasone

-less than 1% bioavailability in oral form bc of first-pass effect
-plasma binding is more than 99% (less than 1% of drug available)
-systemic adminstation = side effects (hypercorticism)

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Inhaled fluticasone

-absolute bioavailability (~10%)
-safe for children under 1

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Aystemic application of inhaled medicines

-300-500 million alveoli in lungs
-huge surface area of lungs

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Alveoli

-surrounded by lung capillaries
-thin walls for gas exchange (good for absorption)
-nonciliated

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Respiratory tract regions

-extrathoracic (head and neck)
-upper bronchial region (trachea and bronchi)
-lower bronchial region (braonchioles)
-alveolar region

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Bronchi

-large ciliated airways

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bronchioles

-small ciliated airways

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Particle deposition mechanisms

-diffusional transport
-inertial transport
-gravitational transport

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diffusional transport

-ultrafine particles
-alveoli
-tend to be exhaled without depositing
-alveolar region

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Gravitational transport

-sedimentation
-slightly bigger particles than diffusional
-increase with diameter and density
-bronchial and alveolar region

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Inertial transport

-impaction
-driven by momentum
-increase with particle velocity, diameter, density
-extrathoracic region

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Sedimentation increases with:

-density
-acceleration due to gravity
-diameter
-slip correction factors

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Sedimentation decreases with:

-shape factors
-viscosity

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sedimentation equation

-terminal settling velocity

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Aerodynamic diameter (Dae)

-diameter of particle with unit mass density of 1g/cm3 that would settle at the same velocity as particle of interest
-EQUATION SLIDE 10

=(density)^0.5 x Dgeo

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Particles with aerodynamic diameter > 5 um

-deposit in upper airways
-due to inertial impaction

particles with aerodynamic diameter 1-5 um

-deposit in lower airways

particles with aerodynamic diameter <1 um

-exhaled

Defense mechanisms of the upper airways (head airways)

-filtering mechanisms in nasal cavity
-trap and eliminate large particles
=sneezing and coughing

Defense mechanisms of conducting airways (lung airways)

-mucocilliary escalator
-IgA

Defense mechanisms of alveoli

-alveolar macrophages
-immunologic mechanisms: T and B lymphocytes; IgG

Types of aerosols: liquid droplets

-pressurized meter-dose inhalers (pMDIs) -nebulizers

types of aerosols: dry particles

-dry powder inhalers (DPIs)

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

-small volume of pressurized drug dispersion is isolated in a metering chamber -released through spray orifice -drug propelled from container, forming spray droplets after equilibriating with atmospheric pressure

pMDI pros/cons

-need good inhalation technique -lung deposition efficiency is typically low: 5-20% -high droplet velocity leads to extensive deposition of drug in oral areas (80%) -drug/solvent compatibility issues with propellant -only suitable for low-dose medications -less expensive

components of pMDI

-drug -propellant (CFC or HFA) -cosolvent (ethanol) -surfactant (sorbitan trioleate, oleic acid, lecithin)

Nebulizers

-generate droplets of drug dispersion using ENERGY from compressed air or piezoelectric ceramics -delivered via INSPIRATORY flow -suitable for treatment of young and elederly patients and emergency treatment

Jet nebulizers

-more time consuming than pMDIs -require hygienic maintenance of equipment -bulky -low efficiency (10-15% of drug deposited)

New nebulizers

-smaller than traditional jet nebulizers -higher delivery efficiency -lower residues -vibration mesh nebulizer and soft mist inhaler

Dry powder inhalers (DPI)

-dry particles in inhaler device -aerosol of dry powder created by airflow carries particles to lungs -deposited dose 5-40% based on formulation, device, and airflow

DPI uses

-asthma, COPD, lung infections -insulin

Breath-actuated passive devices (passive DPI)

-powder aerosols generated by patients' inspiratory airflow -performance of a device could be highly variable among patients -passive

Power-assisted active devices (active DPI)

-mechanical or electrical energy generates powder aerosols -less dependent on patient's inspiration capability -active

single unit-dose DPI

-smaller inhaler -simple design

multiple unit-dose

-convenient for frequent use -inhaler larger -design is complex

Particle production

-mechanical milling -spray drying

jet milling (mechanical milling)

-apply mechanical forces to break up particles -particles are typically cohesive with high surface energy and high electrostatic charge -POOR flowability and POOR aerosolization performance

Spray drying

-drug dissolved into solvent -atomized into small droplets -dried by hot airflow through solvent evaporation

Particle interaction

-van der waals -electrostatic (significant in dry conditions) -capillary forces (signififcant for hygroscopic particles at high humidity -mechanical interlocking

carrier-based DPI formulations

-act as filler for low-dose drugs -improve flowability

Particle deposition is influenced by

-particle geometric diameter -density -morphology -surface energy -electrostatic charge -hygroscopicity

Aerosol performance depends on carrier properties:

-particle geometric diameter -morphology -surface energy -electrostatic charge -drug to carrier ratio -addition of additives