PROPELLANTS

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PROPELLANTS

• BY
• MADHU BURRA
• (M PHARM II- SEM)
• DEPARTMENT OF INDUSTRIAL PHARMACY
• UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
• KAKATIYA UNIVERSITY,
• WARANGAL - 506009

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CONTENTS

• INTRODUCTION
• CLASSIFICATION
• LIQUEFIED GASES
• COMPRESSED GASES
• NOMECLATURE
• DESTRUCTION OF OZONE
• CONCLUSION
• REFERENCES

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INTRODUCTION

• Pharmaceutical aerosols are defined as products
  containing therapeutically active ingredients
  dissolved, suspended, or emulsified in a
  propellant or a mixture of solvent and
  propellant, intended for
• topical administration, for administration
  into the body cavities, intended for
  administration orally or nasally as fine solid
  particles or liquid mists via the respiratory
  system.

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Components of an Aerosol

• Propellant
• Container
• Valve and actuator
• Product concentrate

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PROPELLANTS

• The propellant is generally regarded as the heart
  of the aerosol package. It is responsible for
  development of pressure within the container,
  supplying the necessary force to expel the
  product when the valve is opened.
• The propellant also acts as a solvent and as a
  diluent and has much to do with determing the
  characteristics of the product as it leaves the
  container.

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CLASSIFICATION

• Liquefied gases
• Chlorofluorocarbons (CFCs)
• Hydro chlorofluorocarbons (HCFCs)
• Hydro fluorocarbons (HFCs)
• Hydrocarbons
• Compressed gases
• Nitrogen (N2)
• Nitrous oxide (N2O)
• Carbon dioxide (CO2)

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Liquefied - gases

• Liquefied gases have been widely used as
  propellants for most aerosol products.
• Since they are gases at room temperature and
  atmospheric pressure. However, they can liquefied
  easily by lowering the temperature or by
  increasing the pressure.
• When a liquefied gas propellant is placed into a
  sealed container, it immediately separates into a
  liquid and a vapor phase.
• The pressure exerted against the liquid phase is
  sufficient to push the latter up a dip tube and
  against the valve.
• When the valve is opened, the liquid phase is
  emitted i.e., the pressure with in the container
  is decreased. Immediately a sufficient number of
  molecules change from liquid state to the vapor
  state and restore the original pressure

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CHLOROFLUOROCARBONS (CFCS)

• chlorofluorocarbons (CFCs) are
  inert, non toxic, non-inflammable used
  for oral and inhalation aerosols.
• Among the Chlorofluorocarbons trichlorofluorometha
  ne (Propellant 11), dichlorodifluoromethane
  (Propellant 12) and dichlorotetrafluoroethane
  (Propellant 114) were initially widely used in
  pharmaceutical aerosols.
• Liquefied gases provide a nearly constant
  pressure during packaging operation and have
  large expansion ratio.

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Conti.

• Several of the fluorinated hydrocarbons have an
  expansion ratio of about 240 , that is 1 ml of
  liquefied gas will occupy a volume of app. 240 ml
  if allowed to vaporize.
• These compounds have been implicated in causing a
  depletion of the ozone layer and for
  responsibility for the global warming effect .
• In 1974, the EPA, FDA, and CPSC announced a ban
  on the use of CFCs, namely propellants 11, 12,
  and 114, in most aerosol products. Certain
  pharmaceutical aerosols for inhalation use (MDIs)
  were exempted from this ban.

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NOMENCLATURE

• To refer easily to the Fluorinated hydrocarbons a
  relatively simple system of nomenclature was
  developed by the American Society of
  Refrigerating Engineers in 1957.
• According to this all propellants are designated
  by three digits(000).
• The first digit is one less than the number of
  carbon atoms in the compound (C-1).
• The second digit is one more than the number of
  hydrogen atoms in the compound (H1).
• The last digit represents the number of fluorine
  atoms (F).

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Conti.

• The number of chlorine atoms (for CFCS) in the
  compound is found by subtracting the sum of the
  fluorine and the hydrogen atoms from the total
  number of atoms that can be added to saturate the
  carbon chain.
• In the case of isomers , the letter a,b,c ,etc
  follows the number.
• Examples

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PHYSICAL PROPERTIES

• Solubility- Non polar
• Boiling point- below 240C
• Density - gt1
• Vapor pressure

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VAPOR PRESSURE

• It is defined as the pressure exerted by a liquid
  in equilibrium with its vapor.
• It is dependent on temperature and is independent
  of quantity. i.e. the vapor pressure of a pure
  material is the same for 1 g or 1 ton of the
  compound.
• The vapor pressure ranges from about 13.4 psia
  for propellant 11 to about 85 psia for propellant
  12.
• Vapor pressure between these values may be
  obtained by blending propellant 11 with
  propellant 12 and propellant 12 with propellant
  114.

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Conti

• The vapor pressure of a mixture of propellants
  can be calculated by using Raoults law.
• Pa na/nanb POa
• Pb nb/nanb Pob
• Where Pa and Pb are partial pressures of
  components a and b,
• na and nb are mole fraction of a and b,
• POa and Pob are the vapor pressure of pure
  compound

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BLENDS OF CHLOROFLUOROCARBON PROPELLANTS
PROPELLANT BLEND COMPOSITION VAPOR PRESSURE (psig) 700F DENSITY (g/ml)700F
12/11 12/11 12/114 12/114 12/114 12/114 5050 6040 7030 4060 4555 5545 37.4 44.1 56.1 39.8 42.8 48.4 1.412 1.396 1.368 1.412 1.405 1.390
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PROPERTIES OF CHLOROFLUOROCARBONS (CFCS)
PROPERTY TRICHLORO MONOFLUORO METHANE DICHLORO DIFLUORO METHANE DICHLORO TETRA FLUORO METHANE
Molecular formula Numerical designation Molecular weight Boiling point(1atm) Vapor pressure(psia) Liquid density (gm/ml) Solubility in water (wt ) 0F 0C 700F 1300C 700C 1300F 770F CCl3F 11 137.28 74.7 23.7 13.4 39.0 1.485 1.403 0.11 CCl2F2 12 120.93 -21.6 -29.8 84.9 196.0 1.325 1.191 0.028 CClF2CClF2 114 170.93 38.39 3.55 27.6 73.5 1.468 1.360 0.013
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CHEMICAL PROPERTIES

• Hydrolysis
• Reaction with alcohol- All propellants except
  propellants 11 are stable in presence of alcohol.

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Advantages

• Lack of inhalation toxicity
• Lack of flammability and explosiveness
• High chemical stability except P- 11
• High purity

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Disadvantages

• Destructive to atmospheric Ozone
• Contribute to greenhouse effect
• High cost

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Destruction of Ozone

• Ozone can be destroyed by a number of free
  radical catalysts, the most important of which
  are the atomic chlorine (Cl), hydroxyl radical
  (OH), the nitric oxide radical (NO) and
  bromine (Br).
• Chlorine is found in certain stable organic
  compounds, especially chlorofluorocarbons (CFCs),
  which may find their way to the stratosphere
  without being destroyed in the troposphere due to
  low reactivity. Once in the stratosphere, the Cl
  atoms are liberated from the parent compounds by
  the action of ultraviolet light, and can destroy
  ozone molecules through a variety of catalytic
  cycles.

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Conti

• CFCl3 h? ? CFCl2 Cl
• Cl O3 ? ClO O2
• ClO O ? Cl O2
• In sum O3 O ? O2 O2
• gtIncrease rate of recombination of oxygen,
  leading to an overall decrease in the amount of
  ozone.

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Conti

• It is calculated that a CFC molecule takes an
  average of 15 years to go from the ground level
  up to the upper atmosphere, and it can stay there
  for about a century, destroying up to 100,000
  ozone molecules during that time.

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Ozone hole in September 2006
Largest hole in the record. Size of North
America

September 16
is "World Ozone Day"
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Consequences of Ozone depletion

• Since the ozone layer absorbs UVB ultraviolet
  light from the Sun, ozone layer depletion is
  expected to increase surface UVB levels.
• Possible linked to higher incidence of skin
  cancer.
• Lead to decrease of crop yield.

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HYDROCARBONS

• These are used in topical pharmaceutical
  aerosols.
• They are preferred for use as a propellant over
  the fluorinated hydrocarbon based on their
  environmental acceptance and their lesser cost.
  However , they are flammable and explosive.
• Propane, butane and isobutane are generally used
  as propellants.

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Conti

• They can be blended with one another and with the
  fluorocarbons to obtain the desired vapor
  pressure and or density.
• Since they are flammable, they can be blended
  with propellant 22,which is not flammable, to
  produce a non flammable product or one with less
  flammability than the hydrocarbon propellants.
• Propellant 142 and 152 can also be used to reduce
  the flammability of the overall propellant blend
  and the product.

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FLAMMABILITY OF PROPELLANT 22 BLENDS
Flammable component Non flammable below this concentration (wt )
Propellant 142 Propellant 152 Dimethyl ether Hydrocarbons 70 24 9 5-6
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PROPERTIES OF HYDROCARBONS AND ETHERS
PROPERTY PROPANE ISOBUTANE N-BUTANE DIMEHTYL ETHER
Molecular formula Molecular weight Boiling point(0F) Vapor pressure (psig at 700F ) Liquid density (gm/ml) Flash point(0F) C3H8 44.1 -43.7 110.0 0.50 -156 C4H10 58.1 10.9 30.4 0.56 -117 C4H10 58.1 31.1 16.5 0.58 -101 CH3OCH3 46.1 -13 63.0 0.66 --
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Advantages

• Inexpensive
• Minimal ozone depletion
• Negligible greenhouse effect
• Excellent solvents
• Non toxic and non reactive

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Disadvantages

• Flammable

• Aftertaste
• Unknown toxicity following inhalation
• Low liquid density

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HYDROCHLOROFLUOROCARBONS AND HYDROFLUOROALKANES

• Several new liquefied gas materials have been
  developed to replace the CFCS as propellants.
• Propellant 134a and propellant 227 have been
  developed as a substitutes for propellant 12 in
  MDIs and have survived many of the short and
  long term toxicities.
• To date , no suitable replacement has been found
  for propellants 11 and 114. propellant 11 is used
  to form a slurry with the active ingredient and
  dispensing agent. This is impossible to
  accomplish with propellants 134a and P-227

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Conti..

• The HFCS are extremely poor solvents and will
  not dissolve a sufficient amount of the currently
  used FDA-approved surfactants (oleic acid,
  sorbitan, trioleate, and Soya lecithin).
• HFC propellants are not compatible with some of
  the currently used valves.
• The gaskets and sealing compounds used in MDI
  valves may present compatibility problems to the
  formulator.

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PROPERTIES OF HYDROFLUOROCARBONS (HFCS)
PROPERTY TETRAFLUORO ETHANE HEPTAFLUORO PROPANE
Molecular formula Numerical designation Molecular weight Boiling point(1atm) Vapor pressure(psia) Liquid density (gm/ml) Solubility in water Flammability 0F 0C 700F 1300C 21.10 W/W CF3CH2F 134a 102 -15.0 -26.2 71.1 198.7 1.22 0.150 Non flammable CF3CHFCF3 227 170 -3.2 -16.5 43 at (200) --- 1.41 0.058 Non flammable
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PROPERTIES OF HYDROCHLOROFLUOROCARBONS
PROPERTY DIFLUORO ETHANE
Molecular formula Numerical designation Molecular weight Boiling point (1 atm) Vapor pressure (psia) Liquid density (g/ml) Solubility in water (wt ) 0F 0C 700F 1300F 700F 770F CH3CHF2 152a 66.1 -12.0 -11.0 63.0 176.3 0.91 lt1.0
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Advantages

• Low inhalation toxicity
• High chemical stability
• High purity
• Not ozone depleting

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Disadvantages

• Poor solvents
• Minor greenhouse effect
• High cost

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COMPRESSED GASES

• The compressed gases such as nitrogen , nitrous
  oxide and carbon dioxide have been used as
  aerosol propellants. Depending on the nature of
  the formulation and the type of compressed gas
  used, the product can be dispensed as a fine
  mist, foam, or semisolid.
• However , unlike the liquefied gases, the
  compressed gases possess little expansion ratio
  (3-10 times) and will produce a fairly wet spray
  and foams that are not as stable as liquefied gas
  foams.

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Conti..

• This system has been used for the most part to
  dispense food products and for nonfoods, to
  dispense the product in its original form as a
  semisolid.
• Compressed gases have been used in products such
  as dental creams, hair preparations , ointments,
  and aqueous anti septic and germicidal aerosols
  and are extremely useful in contact lens cleaner
  saline solution and barrier systems.

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PROPERTIES OF COMPRESSED GASES
PROPERTY CARBON DIOXIDE NITROUS OXIDE NITROGEN
Molecular formula Molecular weight Boiling point(0F) Vapor pressure (psia, 700F) Solubility in water, 770F Density (gas) gm/ml CO2 44 -109 852 0.7 1.53 N2O 44 -127 735 0.5 1.53 N2 28 -320 492 0.014 0.96699
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Advantages

• Low inhalation toxicity
• High chemical stability
• High purity
• Inexpensive
• No environmental problems

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Disadvantages

• Require use of a nonvolatile co-solvent
• Produce course droplet sprays
• Pressure falls during use

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CONCLUSION

• The stage has been set so that use of the
  fluorocarbons is severely limited and their use
  will become increasingly prohibitive.
• Hydrofluoroalkanes provide a safe alternative to
  CFCS as propellants in aerosols, but their
  physicochemical properties have required
  extensive redevelopment of the entire product.
• Hydrofluoroalkanes are not environmentally
  neutral and contribute to hydrocarbon emissions,
  global warming and acid rain.

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References

• Ansels, pharmaceutical dosage forms and drug
  delivery systems, 8th edition
• Remington , " The science and practice of
  pharmacy , 21st edition
• Leon. Lachman, The Theory and Practice of
  Industrial Pharmacy, 3rd edition
• Gilbert S.Banker, pharmaceutical dosage forms
  disperse systems volume 2 2nd edition
• Bentley, Text book of pharmaceutics, 8th
  edition
• Indian Pharmacopoeia, 2007, Vol-2
• www.sciencedirectory.com
• www.wikipedia.com
• www.appspharmaceutica.com

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THANK YOU