Exam 3- Lecture 6: Pulmonary Drug Delivery II

What do dry powder inhalers (DPIs) utilize?

Internally contained individual dose of micronized dry particles to be inhaled are stored in separate enclosures on a cartridge

What is a mechanical actuator employed to do?

Break an enclosure (usually a polymer blister) exposing the individual powdered dose to the inhalation port

What are dry particles formulated in DPIs typically?

1-5 micrometer range, which is ideal, but under lower flow rates, these particles are subject to physical, non-covalent forces (Van der Waals & electrostatic) making them highly likely to agglomerate (or aggregation)

How do DPIs resolve the agglomeration issues?

Employ large, inert excipients called carrier particles that improve flow ability & uniformity of particle size by reducing cohesion

What is the most common carrier particle?

Lactose monohydrate

What happens to carrier particles/API constructs upon inhalation?

Will be dispersed & carried toward mouthpiece of device & near end, contact some turbulent inducing structure (grids, channels, baffles)

• Contact w/ these structures overcomes adhesive forces b/w carrier particles & API allowing only API to be inhaled

What do DPIs remove the need for?

Patient coordination b/w actuation & inhalation, as well as use of propellants, but depend highly on an individual patient’s inspiratory flow rates

What do higher rates of inspiratory flow produce?

Greater turbulence & improve flow ability & dispersion of individual drug particles

What do low rates of inspiratory lead to?

Poor dispersion causing particles to stick together & result in increased deposition in oropharyngeal region of airways

What is the minimum size of particles likely for low rates of inspiration?

>5 micrometers → innertial impaction

Would u recommend DPIs to patients w/ COPD, bronchitis, etc?

No- lungs functioning improperly

What do nebulizers convert?

Liquid drug formulation into an aerosol particle, enabling passive pulmonary delivery & remove synchronicity/coordination required for DPIs/MDIs

Who may benefit from nebulizers?

Elderly, children, acute respiratory attacks

What is generation of aerosol particles dependent on?

Device being used

What do jet nebulizers utilize?

Compressed gas to create a shearing force breaking a liquid, drug-containing solution or suspension into aerosols able to be inhaled based on patient’s inspiratory flow

What do ultrasonic nebulizers utilize?

Piezoelectric element that vibrates at a high frequency (high MHz range) creating ultrasonic waves that pass through a liquid drug formulation creating a wave form & causing aerosol generation at liquid-air interfaced

• aerosols are inhaled during patient’ inspiration period

What do droplets/aerosols produced by nebulizers typically fall in?

1-5 micrometers range, but will have greater size distribution relative to MDIs/DPIs

What can inefficient control of particle size distribution may result in?

Drug loss or inadvertent oropharyngeal deposition

What are nebulizers relative to other inhalation devices?

Inefficient delivery wise, only 10-20% of total drug dose is likely to reach deep lungs & may require a higher dose or extended time of administration

What are nebulizers also relative to other devices?

Formulation of drug is flexible

• Nebulizers are amenable to both solution & suspension, which is suitable for both poorly soluble drugs & drugs sensitive to shear stres