The document discusses propellants used in pharmaceutical aerosols, emphasizing their definition, classification, and the role they play in aerosol delivery systems. It details the environmental impact of chlorofluorocarbons (CFCs), their ban due to ozone depletion, and alternatives like hydrocarbons and hydrofluorocarbons (HFCs). The document concludes with a focus on compressed gases and their lesser expansion capabilities compared to liquefied gases.

1. PROPELLANTSPROPELLANTS
BYBY
MADHU BURRA
(M PHARM II- SEM)(M PHARM II- SEM)
DEPARTMENT OF INDUSTRIAL PHARMACYDEPARTMENT OF INDUSTRIAL PHARMACY
UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCESUNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
KAKATIYA UNIVERSITY,KAKATIYA UNIVERSITY,
WARANGAL - 506009WARANGAL - 506009

2. CONTENTSCONTENTS
 INTRODUCTIONINTRODUCTION
 CLASSIFICATIONCLASSIFICATION
– LIQUEFIED GASESLIQUEFIED GASES
– COMPRESSED GASESCOMPRESSED GASES
 NOMECLATURENOMECLATURE
 DESTRUCTION OF OZONEDESTRUCTION OF OZONE
 CONCLUSIONCONCLUSION
 REFERENCESREFERENCES

3.  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”.
INTRODUCTION

4. Components of an AerosolComponents of an Aerosol
 PropellantPropellant
 ContainerContainer
 Valve and actuatorValve and actuator
 Product concentrateProduct concentrate

5. PROPELLANTS
 The propellant is generally regarded as theThe propellant is generally regarded as the
heart of the aerosol package. It isheart of the aerosol package. It is
responsible for development of pressureresponsible for development of pressure
within the container, supplying thewithin the container, supplying the
necessary force to expel the product whennecessary force to expel the product when
the valve is openedthe valve is opened ..
 The propellant also acts as a solvent andThe propellant also acts as a solvent and
as a diluent and has much to do withas a diluent and has much to do with
determing the characteristics of the productdeterming the characteristics of the product
as it leaves the container.as it leaves the container.

6. CLASSIFICATIONCLASSIFICATION
 Liquefied gasesLiquefied gases
 Chlorofluorocarbons (CFC’s)Chlorofluorocarbons (CFC’s)
 Hydro chlorofluorocarbons (HCFC’s)Hydro chlorofluorocarbons (HCFC’s)
 Hydro fluorocarbons (HFC’s)Hydro fluorocarbons (HFC’s)
 HydrocarbonsHydrocarbons
 Compressed gasesCompressed gases
 Nitrogen (NNitrogen (N22 ))
 Nitrous oxide (NNitrous oxide (N22 O)O)
 Carbon dioxide (COCarbon dioxide (CO22 ))

7. Liquefied - gasesLiquefied - 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

8. CHLOROFLUOROCARBONSCHLOROFLUOROCARBONS
(CFC’S)(CFC’S)
 chlorofluorocarbons (CFC’s) are inert,
non toxic, non-inflammable used for oral
and inhalation aerosols.
 Among the Chlorofluorocarbons
trichlorofluoromethane (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.

9. Conti….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.

10. NOMENCLATURENOMENCLATURE
 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
(H+1).
 The last digit represents the number of
fluorine atoms (F).

11. Conti….Conti….
 The number of chlorine atoms (for CFC’S) 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 :

12. PHYSICAL PROPERTIESPHYSICAL PROPERTIES
 Solubility- Non polar
 Boiling point- below 240
C
 Density - >1
 Vapor pressure

13. VAPOR PRESSUREVAPOR 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.

14. Conti…Conti…
 The vapor pressure of a mixture of propellants can
be calculated by using Raoult’s law.
Pa = [na/na+nb] PO
a
Pb =[nb/na+nb] P
o
b
Where Pa and Pb are partial pressures of
components a and b,
na and nb are mole fraction of a and b,
PO
a and P
o
b are the vapor pressure of pure compound

15. BLENDS OFBLENDS OF
CHLOROFLUOROCARBONCHLOROFLUOROCARBON
PROPELLANTSPROPELLANTS
PROPELLANT
BLEND
COMPOSITI
ON
VAPOR
PRESSURE
(psig) 700
F
DENSITY
(g/ml)700
F
12/1112/11
12/1112/11
12/11412/114
12/11412/114
12/11412/114
12/11412/114
50:5050:50
60:4060:40
70:3070:30
40:6040:60
45:5545:55
55:4555:45
37.437.4
44.144.1
56.156.1
39.839.8
42.842.8
48.448.4
1.4121.412
1.3961.396
1.3681.368
1.4121.412
1.4051.405
1.3901.390

16. PROPERTIES OFPROPERTIES OF
CHLOROFLUOROCARBONS (CFC’S)CHLOROFLUOROCARBONS (CFC’S)
PROPERTY TRICHLORO
MONOFLUOR
O METHANE
DICHLOR
O
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 %)
0
F
0
C
700
F
1300
C
700
C
1300
F
770
F
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

17. CHEMICAL PROPERTIESCHEMICAL PROPERTIES
 HydrolysisHydrolysis
 Reaction with alcohol- All propellantsReaction with alcohol- All propellants
except propellants 11 are stable inexcept propellants 11 are stable in
presence of alcohol.presence of alcohol.

18. AdvantagesAdvantages
 Lack of inhalation toxicityLack of inhalation toxicity
 Lack of flammability andLack of flammability and
explosivenessexplosiveness
 High chemical stability except P- 11High chemical stability except P- 11
 High purityHigh purity

19. DisadvantagesDisadvantages
 Destructive to atmospheric OzoneDestructive to atmospheric Ozone
 Contribute to “greenhouse effect”Contribute to “greenhouse effect”
 High costHigh cost

20. Destruction of OzoneDestruction 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.

21. Conti…Conti…
CFCl3 + hν → CFCl2 + Cl
Cl + O3 → ClO + O2
ClO + O → Cl + O2
In sum O3 + O → O2 + O2
=>Increase rate of recombination of oxygen,
leading to an overall decrease in the
amount of ozone.

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

23. Ozone hole in September 2006Ozone hole in September 2006
“Largest hole in the record.
~Size of North America
September 16 is "World Ozone Day"

24. Consequences of Ozone depletionConsequences of Ozone depletion
 Since the ozone layer absorbs UVBSince the ozone layer absorbs UVB
ultraviolet light from the Sun, ozoneultraviolet light from the Sun, ozone
layer depletion is expected to increaselayer depletion is expected to increase
surface UVB levels.surface UVB levels.
 Possible linked to higher incidence ofPossible linked to higher incidence of
skin cancer.skin cancer.
 Lead to decrease of crop yield.Lead to decrease of crop yield.

25. HYDROCARBONSHYDROCARBONS
 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.

26. Conti…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.

27. FLAMMABILITY OF PROPELLANT 22FLAMMABILITY OF PROPELLANT 22
BLENDSBLENDS
Flammable componentFlammable component Non flammable belowNon flammable below
this concentration (wtthis concentration (wt
%)%)
Propellant 142Propellant 142
Propellant 152Propellant 152
Dimethyl etherDimethyl ether
HydrocarbonsHydrocarbons
7070
2424
99
5-65-6

28. PROPERTIES OF HYDROCARBONS ANDPROPERTIES OF HYDROCARBONS AND
ETHERSETHERS
PROPERTY PROPANE ISOBUTAN
E
N-
BUTANE
DIMEHTYL
ETHER
Molecular
formula
Molecular
weight
Boiling point(0
F)
Vapor pressure
(psig at 700
F )
Liquid density
(gm/ml)
Flash point(0
F)
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
--

29. AdvantagesAdvantages
 InexpensiveInexpensive
 Minimal ozone depletionMinimal ozone depletion
 Negligible “greenhouse effect”Negligible “greenhouse effect”
 Excellent solventsExcellent solvents
 Non toxic and non reactiveNon toxic and non reactive

30. DisadvantagesDisadvantages
 FlammableFlammable
 AftertasteAftertaste
 Unknown toxicity following inhalationUnknown toxicity following inhalation
 Low liquid densityLow liquid density

31. HYDROCHLOROFLUOROCARBONSHYDROCHLOROFLUOROCARBONS
AND HYDROFLUOROALKANESAND HYDROFLUOROALKANES
 Several new liquefied gas materials have been
developed to replace the CFC’S as propellants.
 Propellant 134a and propellant 227 have been
developed as a substitutes for propellant 12 in
MDI’s 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

32. Conti..Conti..
 The HFC’S 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.

33. PROPERTIES OFPROPERTIES OF
HYDROFLUOROCARBONS (HFC’S)HYDROFLUOROCARBONS (HFC’S)
PROPERTY TETRAFLUORO
ETHANE
HEPTAFLUOR
O PROPANE
Molecular formula
Numerical designation
Molecular weight
Boiling point(1atm)
Vapor pressure(psia)
Liquid density (gm/ml)
Solubility in water
Flammability
0
F
0
C
700
F
1300
C
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

34. PROPERTIES OFPROPERTIES OF
HYDROCHLOROFLUOROCARBONSHYDROCHLOROFLUOROCARBONS
PROPERTY DIFLUORO
ETHANE
Molecular formula
Numerical designation
Molecular weight
Boiling point (1 atm)
Vapor pressure (psia)
Liquid density (g/ml)
Solubility in water (wt %)
0
F
0
C
700
F
1300
F
700
F
770
F
CH3CHF2
152a
66.1
-12.0
-11.0
63.0
176.3
0.91
<1.0

35. AdvantagesAdvantages
 Low inhalation toxicityLow inhalation toxicity
 High chemical stabilityHigh chemical stability
 High purityHigh purity
 Not ozone depletingNot ozone depleting

36. DisadvantagesDisadvantages
 Poor solventsPoor solvents
 Minor “greenhouse effect”Minor “greenhouse effect”
 High costHigh cost

37. COMPRESSED GASESCOMPRESSED 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.

38. Conti..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.

39. PROPERTIES OF COMPRESSEDPROPERTIES OF COMPRESSED
GASESGASES
PROPERTY CARBON
DIOXIDE
NITROUS
OXIDE
NITROGEN
Molecular formula
Molecular
weight
Boiling point(0
F)
Vapor pressure
(psia, 700
F)
Solubility in water,
770
F
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

40. AdvantagesAdvantages
 Low inhalation toxicityLow inhalation toxicity
 High chemical stabilityHigh chemical stability
 High purityHigh purity
 InexpensiveInexpensive
 No environmental problemsNo environmental problems

41. DisadvantagesDisadvantages
 Require use of a nonvolatile co-Require use of a nonvolatile co-
solventsolvent
 Produce course droplet spraysProduce course droplet sprays
 Pressure falls during usePressure falls during use

42. CONCLUSIONCONCLUSION
 The stage has been set so that use of theThe stage has been set so that use of the
fluorocarbons is severely limited and their usefluorocarbons is severely limited and their use
will become increasingly prohibitive.will become increasingly prohibitive.
 Hydrofluoroalkanes provide a safe alternativeHydrofluoroalkanes provide a safe alternative
to CFC’S as propellants in aerosols, but theirto CFC’S as propellants in aerosols, but their
physicochemical properties have requiredphysicochemical properties have required
extensive redevelopment of the entire product.extensive redevelopment of the entire product.
 Hydrofluoroalkanes are not environmentallyHydrofluoroalkanes are not environmentally
neutral and contribute to hydrocarbonneutral and contribute to hydrocarbon
emissions, global warming and acid rain.emissions, global warming and acid rain.

43. References
1)1) Ansel’s, “ pharmaceutical dosage formsAnsel’s, “ pharmaceutical dosage forms
and drug delivery systems”, 8and drug delivery systems”, 8thth
editionedition
2)2) Remington , " The science and practiceRemington , " The science and practice
of pharmacy “ , 21of pharmacy “ , 21stst
editionedition
3)3) Leon. Lachman, “The Theory andLeon. Lachman, “The Theory and
Practice of Industrial Pharmacy”, 3Practice of Industrial Pharmacy”, 3rdrd
editionedition
4)4) Gilbert S.Banker, “ pharmaceuticalGilbert S.Banker, “ pharmaceutical
dosage forms” disperse systems;dosage forms” disperse systems;
volume 2; 2volume 2; 2ndnd
editionedition
5)5) Bentley, “ Text book of pharmaceutics”,Bentley, “ Text book of pharmaceutics”,
88thth
editionedition
6)6) ““Indian Pharmacopoeia”, 2007, Vol-2Indian Pharmacopoeia”, 2007, Vol-2
7) www.sciencedirectory.com
8) www.wikipedia.com