Download 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 Therapy
 Has been used for many years
 Many 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 Therapy
 Originally, 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 Therapy
 Drugs administered via the respiratory system
(inhalation therapy) can be delivered either orally or
nasally.
 These products can be developed as a:
 nebulizer/atomizer
 dry powder inhaler
 nasal inhaler
 metered dose aerosol inhaler
Inhalation Therapy
 Drugs 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 1996
 Dry 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 Inhaler
 consists 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 Aerosols
 Can be formulated:
 spray, foam, and semisolid
 used 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 action
 Circumvention of the first-pass effect and avoidance of
degradation in the GI tract
 Lower 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
medication
 Alternate 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 Package
 Propellant
 Container
 Valve and actuator
 Product 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 ethers
2.
Compressed gases




Chlorofluorocarbon
 Chemically inert
 Flammable
 Non-toxic.
 Expensive when compared with hydrocarbons
(HC).
 Deplete ozone layer.
Hydrocarbon (HC)
 Chemically stable
 No hydrolysis
 Inflammable
 Low order of toxicity
 Less expensive
 Environmentally acceptable
Compressed Gas
 Low expansion power and has no chilling effect.
 Foams produced by them are less stable when compare
with liquefied gas foams
 Widely 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

1.
2.
3.
Metal
Tinplate steel
Aluminum
Stainless steel

a.
b.
Glass
Uncoated
Plastic-coated glass
Tin-Plate Steel
 Materials 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 Containers
 Used 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 Containers
 Limited to those products having lower pressure and lower
percentage of propellant.
 Stronger than metallic container
 Use 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 aerosols
1.
2.
3.
4.
5.
6.
Propellant : tested for vapor pressure, identity, purity
and acceptability.
Valves, actuators and dip tubes : valve acceptance,
delivery rate.
Containers : dimensions, defects in lining, weight of
container.
Weight checking
Leak checking : checking of crimp dimension, leaked
tank testing.
Spray testing : to check valve and spray pattern.