FORMULATION OF PHARMACEUTICAL AEROSOLS Class Compressed gases

CHAPTER 11 Use
 Aerosol is defined as a system that depends on the power of Advantages low inhalation toxicity; high chemical
a compressed or liquified gas to expel the contents from the stability; high purity; inexpensive; no
container environmental problems
 packaging of therapeutically active ingredients in a Disadvantages require the use of nonvolatile co-solvent;
pressurized system produce coarse droplets – only applicable
USES AND APPLICATIONS OF AEROSOLS for dermatological/ topical/ surface sprays;
 Topical convenient, no need to touch skin, minimal pressure fails during use
contamination of the used product Examples CO2 , Nitrogen, NO
 Oral or Lingual provides access to hard-to-reach areas, CONTAINERS
provides access to systemic circulations
 must withstand pressures as high as 140 to 180psig at 130ºF
 Vaginal produces access to hard-to-reach Vaginal areas
Three-piece Tin Plate
 Rectal provide complete surface coverage
 Visible seams make it less appealing
 Nasal access to hard-to-reach areas, minimal dripping
 Incompatible with some propellants and solvents
 Ocular but not applied directly to the eye! only for ocular
Aluminum
device
 Lightweight and seamless, opaque
 Respiratory provide local or systemic action
 Can be screen-printed, therefore visually appealing
ADVANTAGES AND DISADVANTAGES OF AEROSOLS
 Incompatible with some propellants and solvents (can be
Advantages:
epoxy-coated)
 portable
 Easy to fill and crimp
 regarded as easy to use and convenient
 Used for inhalation and topical aerosols
 remaining product is not contaminated during use
Plastic coated glass
 protect unstable drugs from light oxygen and water
 allows level of contents to be seen o compatible with most
 target site need not be touched
aerosol formulations
Disadvantages:
 plastic coating adsorbs “neck shock” during crimping,
o expensive
providing barrier to broken glass
o performance can deteriorate during the life of the product
 poor aesthetic finish, difficult to label, heavy
o limited safety hazards (flammable, pressurized, in advent
 used for inhalation aerosols containing dissolved
inhalation)
drugs
COMPONENTS OF AEROSOL PACKAGE
VALVES
 Propellants
 Containers Valve Functions:
1. opening and closing of product
 Valve
2. delivers container in desired form
 Actuator
3. delivery given amount of medicines
PROPELLANTS TYPES:
 responsible for developing the proper pressure within the Continuous Spray Valve
container and it expels the product when the valve is opened  contains different parts
and aids in the atomization or foam production of the Metering Valve
product  applicable to the dispensing of potent medication
 “heart of aerosol technology” CONTINUOUS SPRAY VALVE PARTS
Class Fluorinated HC  Ferrule or Mounting cup
Use Use oral and inhalation  Valve Body or Housing
Advantages low inhalation toxicity; high chemical  Stem
 Gasket
stability; high purity; excellent solvents
 Spring
Disadvantages ozone depleting; contribute to greenhouse  Dip Tube
effect Ferrule or Mounting cup
Examples trichloromonofluoromethane (#11);  attached to the aerosol or container
dichlorodifluoromethane (#12);  holds valve in place
dichlorotetrafluoroethane (#114  Ferrules are used with glass bottles or small aluminum
Class Hydrocarbons tubes and are usually made from a softer metal such
Use topical aluminum or brass
Advantages Inexpensive; minimal ozone depletion; Valve Body or Housing
negligible greenhouse effect; excellent  below the mounting cup
solvent power  link between dip hole, stem, actuator
Disadvantages flammable; aftertaste; unknown toxicity Stem
following inhalation; low liquid density  made from Nylon but metals such as brass and stainless
Examples n-butane, isobutane, propane steel can also be utilized
  deliver formation in propellant form ACUATORS
Gasket
 placed snugly of stem
 prevents leakage of foam when valve is opened
Spring
 holds gasket in place
 when actuator is depressed and release, it returns the valve
to its closed position
Dip Tube
 housing below the product
 brings foam from the container to valve
METERING VALVE

Metered-Dose Inhalers
 used to minimize the number of administration errors and to
improve the drug delivery of aerosolized particles into the
nasal passageways and respiratory airways
FORMULATION OF AEROSOLS
 Propellant
 Product Concentrate
PROPELLANT
 may be single or a blend of various propellants
 can be compared with other vehicles used in pharmaceutical
formulation
 helps expel the product concentrate in different forms
 wet or dry spray
ACTUATOR  coarse or fine spray
 button used to ensure that aerosols produced is delivered in  stable emulsion foam
proper and desired form PRODUCT CONCENTRATE
 allows for easy opening and closing of the valve  consists of active ingredients or mixture of active ingredients
 integral part of almost every aerosol package and other necessary agents such as solvents, antioxidants,
 aids in producing the required type of product discharge and surfactants
ACTUATOR-TYPES  blend of solvents is used to achieve desired solubility
Spray  type of system selection depends of the ff factors:
 capable of dispensing the stream of product concentrate and physical, chemical and pharmacologic
propellant into relatively small particles by allowing the  properties of AI
stream to pass through various openings (topical use)  site of application
Foam TYPES OF AEROSOL SYSTEMS
 consist large orifices to pass product into relatively large  Solution System
chamber, where it can expand and be dispensed through the  Water-Based System
large orifice  Suspension or Dispersion System
Solid-Stream  Foam System
 dispensing semi-solid products (ointments)  Aqueous Stable Foam
 large openings  Non-aqueous Stable Foams
Special  Quick-Breaking Foam
 accomplish specific purpose  Thermal Foam
 designed medication to deliver at appropriate site of action  Intranasal Aerosols
(nose, eyes, throat, vaginal tract) SOLUTION SYSTEM
 referred as two-phase system and consists of a vapor and
liquid phase
 when the AI’s are soluble in propellant, no other solvent is
requiredamount of propellant used may vary from 5% (foam)
to 95% (inhalation)
WATER-BASED SYSTEM
 relatively large amount of water can be used to replace all or
part of the non-aqueous solvents used in aerosols
 to produce a spray, formulation must consist of a dispersion PRESSURE BURETTE OR LABORATORY FILLING AEROSOLS
of AI’ s and other solvents in an emulsion system in which the
propellant is in external phase three-phase aerosol is formed;
ethanol is added as cosolvent to solubilized some propellant
in water
 “Aquasol” – allows for the dispersion of a fine mist or spray
of active ingredient dissolved in water
SUSPENSION OR DISPERSION SYSTEM
 dispersion of AI in the propellant or a mixture of propellant
 to decrease the rate of settling of the dispersed particles,
various surfactants or suspending agents have been added to
the systems
FOAM SYSTEM
 liquefied propellant is emulsified and is generally found in the
internal phase
 aerosol emulsions are dispersed as foams COLD FILLING APPARATUS
AQUEOUS STABLE FOAM  simpler than the pressure filling apparatus
 lower propellant conc yields wetter foams  all that is needed is an insulated box fitted with copper tubing
 different steroids and antibiotics can be dispensed in this that has been coiled to increase at the area exposed to
manner cooling
 HC and compressed gas can be used as propellants  can be used in metered valve and non-metered valve
NON-AQUEOUS STABLE FOAMS  not to use to fill HC aerosols since an excessive amount of
 may be formulated through the use of various glycols such as propellant escaping and vaporizing may form explosive
polyethylene glycol mixture at lower levels
QUICK-BREAKING FOAM APPARATUS FOR COLD FILLING PROCESS
 the propellant is in the external phase
 when dispensed, the product is emitted as foam, which then
collapses into a liquid
 applicable for topical medication, that can be applied to
limited or large areas w/o use of mechanical force to
dispense the AI
THERMAL FOAM
 warm foam for shaving
 discontinued due to inconvenience of use, expense and lack
of effectiveness and corrosion problems
INTRANASAL AEROSOLS
advantages:
 delivery of metered drug dose COMPRESSED GAS FILLING APPARATUS
 excellent depth penetration into the nasal passageway with  pressure-reducing valve is required
minimal inadvertent penetration into the lungs  attached to the delivery gauge is a flexible hose capable of
 reduced droplet or particle size withstanding about 150 pounds per square inch gauge
 lower dose pressure and fitted with a filling head
 decreased mucosal irritability  use for filling aerosols with compressed gases
 greater flexibility in product formulation QUALITY CONTROL TESTS FOR AEROSOLS
 inhalation aerosol vs intranasal aerosol product is the design  Standard pharmaceutical tests:
of the adaptor  Identity and purity test of the drug
MANUFACTURE OF AEROSOLS  Drug concentration and product fill weight
 low temperature or under high pressure must be available  Stability test
 Pressure Filling Apparatus  Integrity test – no bubbles are release under water at 55C
 Cold Filling Apparatus  Propellant leakage test
 Compressed Gas Filling Apparatus  Product delivery rate – for continuous valves only
PRESSURE FILLING APPARATUS  Flame projection - for continuous valves only
 consists of a pressure burette capable of metering small  Specific Tests
volumes of liquefied gas under pressure into an aerosol  Moisture
container  Particle size determination
 propellant added through the inlet valve located at the top or  Biologic Testing
bottom of the burette
 Toxicity
 trapped air is allowed to escape through the upper valve