Aerosols ILE 5

what are the three methods of drug delivery for aerosols

-metered dose inhalers

-dry powder inhalers

-nebulizers

do aerosols have local or systemic delivery

both

describe local delivery of aerosols

to the respiratory tract performed for the treatment of local disorders

list local disorders for which aerosols are used for

asthma, cystic fibrosis, and COVID-19

describe systemic delivery of aerosols

employed to achieve drug absorption into the systemic circulation

list the advantages of inhaled drug delivery

local delivery, viable alternative to oral delivery, rapid onset, portable and convenient, no contamination, feasible alternative for drugs with erratic pharmacokinetic behavior

describe the advantage of local delivery of aerosols

-minimizes systemic side-effects

-delivered to the site of action where action is needed

describe the advantage of being a viable alternative to oral or parenteral delivery

due to the large surface area of the lungs, the blood supply for gas exchange and the thin nature of the barrier between the lunch and the systemic circulation, the lungs act as a portal for systemic drug absorption

describe the onset as an advantage of aerosols

rapid and beneficial

is portability and convenience and advantage or disadvantage of aerosols

advantage

describe the contamination of aerosols

advantage because the devices are completely sealed which is a safety feature for inhalers

describe disadvantages of aerosols

-coordination is required for MDIs

-improper use can result in drug being delivered in upper airways

-drug deposition to lungs may be impeded in the presence of high volumes of mucus

-physical stability may be problematic

what is the primary function of the respiratory tract

gas exchange

what is a secondary function of the respiratory tract

cleaning and humidifying of the incoming air to prevent damage of this vital organ

what are the conducting airways

trachea, bronchi, and bronchioles

what are the respiratory airways

respiratory bronchioles, alveolar ducts, and alveolar sacs (alveoli)

describe the features of alveoli

-large surface area

-highly vascularized

-gas exchange

-drug absorption

is pulmonary vasculature for respiratory blood flow the same circulation as systemic circulation?

no

describe the respiratory blood flow

the main pulmonary artery starts in the right ventricle, then divides into two branches for the left and right lungs

do drugs absorbed into the pulmonary circulation go through or avoid first-pass hepatic effect?

avoid first-pass metabolism

where can drugs via aerosols possibly be metabolized

in the respiratory tract

list the factors that affect deposition of aerosols

-mode of inhalation

-aerosol properties

-humidity effects on the particle size

what are the most important features of inhalation

-inhaled volume

-flow rate

-breath holding pause maintained at end inspiration

what does MMAD stand for

mass median aerodynamic diameter

what is the vital physical property of aerosols

MMAD

define MMAD

the product of physical diameter and the square root of density

what happens when MMAD is less than 5 micrometers

deposition occurs in the alveolar ducts and alveoli

what happens when MMAD is greater than 5 micrometers

deposition occurs in the oropharynx

do the lungs have a high or low humid environment

high

what results from the high humid environment of the lungs

the deposition of a layer of moisture on the surface of the particle

describe a lipophilic inhaled particle

the absorbed layer of moisture is negligible and does not affect the MMAD

describe a hydrophilic inhaled particle

the absorbed layer of moisture results in the dissolution of the hydrophilic particle and increase in effective particle size and possible deposition within the higher regions of the respiratory tract

list the mechanism that govern the deposition of particles within the respiratory tract

-inertial impaction

-gravitational sedimentation

-brownian diffusion

-electrostatic precipitation

what is inertial impaction

velocity-dependent mechanism and causes most of the particles larger than 6 micrometers to deposit in the upper respiratory tract and in the first-generations of the trachea-bronchial tree

what does the inertia of an airborne particle tend to cause?

travel in its initial path when the supporting airstream is suddenly deflected (turbinate, bifurcate)

what is sedimentation

the gravitational settling of particle and mainly affects particles less than 6 micrometers which deposit in small airways and alveolar ducts

describe gravitational sedimentation

every particle allowed to fall in air will accelerate to a terminal settling velocity where the force of gravity is balanced by the resistance of the air through which the particle is falling according to the stocks law

factors that may increase particle deposition by sedimentation

-increase in particle size

-decrease in airflow

describe brownian diffusion

particle deposition by diffusion or brownian motion predominates for very small particles in the colloidal range and occurs predominantly in the periphery of the lung

describe electrostatic precipitation

the charge on the surface of a particle may affect lung deposition -- the charge on the particles enables interactions within the surface of the respiratory tract that possesses an opposite charge

can the charge on particles also induce interactions with plastic surfaces

yes

how will the induction of an interaction affect the delivery?

may compromise the effective delivery of the particles to the required site within the respiratory tract

how big should particles be for optimal alveolar deposition

generally less than 5 micrometers in diameter, if particles are below this are more likely to reach the alveoli where gas exchange occurs

what is an aerosol

products containing therapeutically active ingredients dissolved, suspended, or emulsified in a propellant (or a mixture of solvent and propellant)

how is the active medication dispersed from an aerosol

finely dispersed mist, foam, or semisolid

what can an aerosol be?

suspension, solution, or emulsion

list the routes of administration of aerosols

oral, nasal, lingual, topical, vaginal, or rectal

how are aerosols different from other dosage forms

the depend on the function of the container, its valve assembly, and an added component (the propellant) for the physical delivery of the medication in proper form

what are the classifications of aerosol products

-space sprays

-surface coating

-aerated sprays

describe a space spray

high amount of propellant that disperses the active ingredients as a finely divided spray with the particle size no larger than 50 micrometers in diameter

examples of space sprays

inhalation, nasal, or sublingual

describe a surface coating aerosol

low amount of propellant that disperses larger particles, generally producing a wet or coarse spray

example of a surface coating aerosol

dermatologic aerosols (topical)

describe an aerated sprays

very low amount of propellant that disperses medicated foams

examples of aerated sprays

vaginal foams or shaving creams

what type of gases make up aerosol propellants

liquified or compressed gases

aerosol formualtion contains what

product concentrate and propellant

what is the product concentrate

the active ingredient as a suspension, solution, or emulsion combined with inactives such as antioxidants, surfactants, and solvents to prepare stable and efficacious product

what is the propellant

a liquified gas or a mixture of liquified gases or a compressed gas and frequently serves as a solvent or vehicle for the product concentrate

what makes up an aerosol system

product concentrate, propellant, container and suitable valve

describe solution aerosols

-product concentrate is dissolved in the propellant/solvent system

-drug may be insoluble due to non-polar nature of propellants

list co-solvents

ethyl alcohol! or PEG, ethyl acetate, hexylene glycol, acetone, glycol ethers

in a solution aerosol, if the concentration of propellant is increased, what happens to the degree of dispersion

the degree of dispersion is increased the spray is finer

describe suspension aerosols

-product concentrate is dispersed in the propellant

-co-solvent is NOT desirable

-suspension is emitted by rapid vaporization of the propellant leaving behind the finally dispersed active ingredients

examples of nasal suspension aerosols

-beta agonists

-steroids

-antibiotics

what can occur in suspension aerosols

formulations are susceptible to caking, agglomeration, particle size growth, and clogging of the valve

characteristics of suspension aerosols

-moisture must be below 200-200 ppm

-1-5 micrometers, no more than 10 particle size

-propellant with minimum drug solubility

-sufficient solution in body fluids to be effective

-sedimentation will be reduced by making densities of the ingredients similar

-non-toxic, biodegradable, and minimally irritating

describe emulsion aerosols

-active ingredients, aqueous/non-aqueous vehicle, surfactant, and propellant

-product can be emitted as stable or quick-breaking foam

-very low amount of propellant used with 90-94% emulsion concentrate

-propellant is part of immiscible phase in internal or external phase

-internal phase, foam is emitted

-external phase, dispensed as spray or quick breaking foam

how does an MDI work

designed to deliver an exact (metered) amount (dose) of medication in a fine mist that can be inhaled directly into the lungs through a single depression of the actuator which causes evacuation of the chamber contents

how is the amount of material discharged regulatedq

by a metered chamber

what controls the integrity of the chamber

dual valve mechanism

what occurs when the outlet valve (actuator) is closed

the chamber is sealed from the atmosphere, however, in this position the chamber is permitted to fill with the contents of the container, to which it is open

advantages of MDIs

-portable, light, and compact

-easy to use

-short treatment time

-same dose

-nothing to mix

-difficult to get dirty

-mature technology

disadvantages of MDIs

-hand-breath coordination required

-pushed by patient, so need proper breathing pattern and breath-hold from patient

-unwanted stuff in mouthpiece may be breathed in

-medicine may hit back of through instead of lungs

-requirement to change from CFCs to HFAs results in formulation issues

what is an add-on device for MDIs

spacers/reservoirs or valved holding chambers

characteristics of add-on devices for MDIs

-slow down droplets

-control inhalation rate

-trap large droplets

-allow droplet evaporation yielding smaller particles

-aid coordination actuation and inhalation

advantages of add-on devices for MDIs

-less medication remains in mouth and more goes in air passages

-increases inhaled medicated by 2-4 times

-allows use of MDI when patient is short of breath

-makes timing of MDI hand-breath coordination easier

disadvantages of add-on devices for MDIs

-larger than MDI alone

-more expensive than MDI alone

-must be put together

-mistake of putting multiple puffs into chamber

-requires cleaning every week

what label should be on ALL aerosols

contents under pressure. do not puncture or incinerate container. do not expose to heat or store at temperatures above 49 Celsius. keep out of reach of children

what labels should be on nasal aerosols

-"avoid inhaling. keep away from eyes or other mucous membranes"

-"use only as directed. intentional misuse by deliberately concentrating and inhaling the contents can be harmful or fatal."

what are dry powder inhalers

used to deliver aerosol medications to the air passages at which the medication inside the DPI is a very small amount of powder in each dose

how to use DPIs

when you take a fast, deep breath through the inhaler, you pull the medication out of the device and into your air passages and DPIs deliver medication to the lungs as you inhale through the device without the use of propellants

what makes up a DPI

-an air inlet

-chamber for the medication to rest before it is breathed-in

-mouthpiece

how do DPIs work

there is a chamber for the powdered medication (less than 5 micrometers) or presented as a capsule that is placed in chamber and the patient takes a fast, deep breath through the mouthpiece to pull in the medication into your air passages without the use of propellants

what happens if you take a slow breath with a DPI

prevents you from receiving the full amount of medication

advantages of DPIs

-small and portable

-built-in dose counter

-breathing in does not need to be coordinated

-quick breathing treatment

disadvantages of DPIs

-full dose is not delivered with slow breathing

-cannot feel medication entering air passages

-room humidity or breathing out may make it difficult to separate medication in future doses

-not available for all medications

-different styles of DPIs is confusing

list the designs of DPIs

-hard gelatin capsule

-blister pack

-drug present within the inhaler

do DPIs use a liquid propellant

no

describe nebulizers

-can be used instead of MDI

-changes a liquid formulation into fine droplets that are inhaled through mouthpiece or mask

-requires of compressed air machine operated by battery

-product contamination is major concern

advantages of nebulizers

-works with any medication

-allows more than one medication to be used at the same time

-minimal patient cooperation/coordination is needed

-useful when patients cannot use MDI or DPI

-medication dose and concentrations can be modified

-normal breathing is used and does not require breath-holding

disadvantages of nebulizers

-treatment times last from 15-25 minutes

-device required may be large or bulky

-power source needed

-medication can get into eyes if using face mask

-assembly and cleaning required