Aerosols

Aerosols Dr. Bridg’ette Israel

Spring 2011

Aerosols Definition: The term aerosol is used to

denote various systems ranging from those of a colloidal nature to systems consisting of pressurized packages. Aerosols have been defined as colloidal systems consisting of very finely subdivided liquid or solid particles dispersed in and surrounded by a gas.

Inhalation TherapyHas been used for many yearsMany scientists have revisited this route of

administration The number of new drug entities delivered by

the inhalation route has increased over the past 5 to 10 years.

This type of therapy also has been applied to delivery of drugs through the nasal mucosa, as well as through the oral cavity for buccal absorption.

Inhalation TherapyOriginally, this type of therapy was used

primarily to administer drugs directly to the respiratory system (treatment of asthma)

Inhalation therapy is now delivering drugs to the bloodstream and their desired site of action.

Proteins (insulins), steroids, cardiac agents, immunizing agents, etc, are being developed for delivery in this manner.

Inhalation TherapyDrugs administered via the respiratory

system (inhalation therapy) can be delivered either orally or nasally.

These products can be developed as a:nebulizer/atomizerdry powder inhalernasal inhalermetered dose aerosol inhaler

Inhalation TherapyDrugs delivered via a nebulizer/atomizer are

generally formulated as aqueous solutions (or suspensions)

They are inhaled by the patient through an atomizer, nebulizer, or other similar devices.

Background Information Dry powders have been used for inhalation therapy

for over 75 years. The active ingredients were packaged in capsules,

representing a single dose of drug. The capsule was punctured and a small amount of

powder fell into a chamber while the patient inhaled. The procedure was repeated until all of the powder

was inhaled. While these dry powders were somewhat popular during the early 1940s–1950s, they fell into disuse with the introduction of the aerosol metered dose inhaler (MDI), which became available around 1955.

Background Information This first generation MDI was formulated

with chlorofluorocarbons (CFC), was compact, and contained epinephrine hydrochloride or albuterol as the active ingredient.

MDIs became very popular for the treatment of asthmatics.

CFC’s began phasing out in 1996Dry powders ~60 doses of active ingredient were

developed and became commercially available from 2000 to 2003.

Several dry powder inhalers currently available include salmeterol, fluticasone, and budesonide.

Mometasone dry powder inhaler is available in Europe while insulin dry powder inhaler is presently in the final stages of development and submitted to the Food and Drug Administration for review.

These dry powder inhalers do not contain a propellant.

They consist of active, very potent drugs that are dispensed from a specially designed package.

An accurate amount of drug as a dry powder is released while the patient inhales deeply.

Nasal Metering Device Produces an aqueous spray consisting of active

ingredient and excipients.The drugs used can act locally within the nasal

mucosa or systemically by passing through the nasal mucosa and enter the general circulation system.

This occurs via numerous capillary vessels present in the mucosa.

These nasal sprays can also be formulated similar to MDIs using propellants and a nasal adapter.

Metered-Dosed Inhaler Developed in the mid 1950’s & became a possible

convenient dosage form for the delivery of medication to the respiratory system.

Atomizers and nebulizers, in many instances did not offer convenience of use, so that administration of drugs by atomizers/nebulizers was generally left to hospital or at-home use.

While many improvements were made to these nebulizers and atomizers, they lacked the convenience of use especially as to their portability and use outside of a hospital and/or home setting.

Metered Dose Inhalerconsists of a pressurized container filled with active

ingredient, excipients and propellant, and a metered-dose valve.

The pressurized container is placed within an oral adapter (mouthpiece), and when the unit is dispensed, an exact amount of drug is expelled in the proper particle size distribution to achieve maximum deposition of drug into the lungs.

The aerosol dosage form (MDI) has become the dosage form of choice for delivery of drugs to the lungs.

Metered dose inhalers are formulated as solutions or suspensions of active drug in a mixture of solvents, dispersing agents, and liquefied gas propellants.

Topical Pharmaceutical AerosolsCan be formulated: spray, foam, and semisolidused to deliver therapeutic agents topically to

the skin surface, rectally, and vaginally

They consist of a liquid, emulsion, or semisolid concentrate and liquefied gas or compressed gas propellant.

Many therapeutically active ingredients have been administered or applied to the body by means of the aerosol dosage form.

This dosage form has been used orally to dispense a variety of agents such as budesonide, salmeterol xinafoate, fluticasone propionate, fenoterol, epinephrine hydrochloride, albuterol, albuterol sulfate, metaproterenol sulfate, cromolyn sodium, flunisolide hemihydrate, ipratropium bromide, beclomethasone dipropionate, and triamcinolone acetonide.

These MDIs were formulated using a CFC propellant and are currently in widespread use in the United States even though the use of CFCs has been phased out throughout the world.

Some exemptions have been granted to Third World Countries and “essential use” exemption has been granted to MDIs, which were commercially available prior to the year 2000.

Oral aerosols have been used mainly for the symptomatic treatment of asthma as well as for the treatment of several other ailments.

These aerosols have been readily accepted by both physician and patient.

Advantages of Aerosol Use Rapid onset of actionCircumvention of the first-pass effect and

avoidance of degradation in the GI tractLower dosage that will minimize adverse

reactions, especially in the case of steroid therapy where most of the steroid reaches the respiratory tract and less is swallowed

Advantages of Aerosol Use Dose titration to individual needs and ideal

for prn medicationAlternate route when therapeutic agent may

interact chemically or physically with other medicinals needed concurrently

Viable alternative when the drug entity exhibits erratic pharmacokinetics upon oral or parenteral administration

Container and valve closure are tamperproof

Components of Aerosol PackagePropellantContainerValve and actuatorProduct concentrate

Propellant Responsible for developing pressure.Expel the product when the valve is opened.Aids in atomization or foam production of

product

Types of Propellants 1. Liquefied gases : Fluorinated hydrocarbons Cholofluorocarbons (CFC) Hydro fluorocarbons Hydrochlorofluorocarbon Hydrocarbons Hydrocarbon ethers2. Compressed gases

ChlorofluorocarbonChemically inertFlammableNon-toxic.Expensive when compared with

hydrocarbons (HC).Deplete ozone layer.

Hydrocarbon (HC)

Chemically stableNo hydrolysisInflammableLow order of toxicityLess expensiveEnvironmentally acceptable

Compressed GasLow expansion power and has no chilling

effect.Foams produced by them are less stable

when compare with liquefied gas foamsWidely used in dispensing food and non-food

products in original form i.e., semisolid.Used as propellants in dental creams, hair

preparations, ointments, antiseptics, germicide aerosols

Containers Metal1. Tinplate steel2. Aluminum3. Stainless steel

Glassa. Uncoatedb. Plastic-coated glass

Tin-Plate SteelMaterials used for the manufacture of aerosol container

must withstand pressure as 140 to 180 psig at 1300 F.These containers consist of a steel plate that has been

electroplated on both sides with tin.The thickness of tin is described in weight.Size of container is measure of diameter and height.Recent development: welded side-seam which eliminates

soldering operation, saves manufacturing time and decreases the possibility of product/container interaction.

Aluminum ContainersUsed to manufacture extruded (seamless) containers.Less danger of incompatibility due to its seamless nature

and greater resistance to corrosion. Inside aluminum containers are coated with organic

materials like epoxy, vinyl, phenolic or polyamide resins to provide additional resistance.

Aluminum containers get corroded by pure water and ethanol.

Stainless Steel Containers• Limited to small size due to production

problems and cost.They are extremely strong and resistant

to most materials.In most cases no internal coating is used.

Glass ContainersLimited to those products having lower pressure and

lower percentage of propellant.Stronger than metallic containerUse of glass allows greater degree of freedom in

design of container.

Two types:a.Plastic coated glass: these containers are protected

by plastic coating that prevents the glass from shattering in the event of breakage.

b.Uncoated glass: low cost and provide clarity by which all the contents of the container can be viewed.

Coating Epoxy or vinyl coating are generally used.Vinyl resin forms tough coating but is

poorly resistant to steam about 2000 C.Epoxy coatings has greater degree or heat

stability hence mixture of above two coating are used.

Quality control of aerosols1. Propellant : tested for vapor pressure, identity,

purity and acceptability.2. Valves, actuators and dip tubes : valve

acceptance, delivery rate.3. Containers : dimensions, defects in lining,

weight of container.4. Weight checking 5. Leak checking : checking of crimp dimension,

leaked tank testing.6. Spray testing : to check valve and spray

pattern.