Transcript PROPELLANTS - Pharmawiki.in

PROPELLANTS
BY
MADHU BURRA
(M PHARM II- SEM)
DEPARTMENT OF INDUSTRIAL PHARMACY
UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
KAKATIYA UNIVERSITY,
WARANGAL - 506009
CONTENTS
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INTRODUCTION
CLASSIFICATION
– LIQUEFIED GASES
– COMPRESSED GASES
NOMECLATURE
DESTRUCTION OF OZONE
CONCLUSION
REFERENCES
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”.
Components of an Aerosol
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Propellant
Container
Valve and actuator
Product concentrate
PROPELLANTS
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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.
CLASSIFICATION
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Liquefied gases
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Chlorofluorocarbons (CFC’s)
Hydro chlorofluorocarbons (HCFC’s)
Hydro fluorocarbons (HFC’s)
Hydrocarbons
Compressed gases
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Nitrogen (N2)
Nitrous oxide (N2O)
Carbon dioxide (CO2)
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
CHLOROFLUOROCARBONS
(CFC’S)
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chlorofluorocarbons (CFC’s) are
non toxic, non-inflammable used
and inhalation aerosols.
inert,
for oral
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.
Conti….
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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.
NOMENCLATURE
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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).
Conti….
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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 :
PHYSICAL PROPERTIES
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Solubility- Non polar
Boiling point- below 240C
Density - >1
Vapor pressure
VAPOR PRESSURE
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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.
Conti…

The vapor pressure of a mixture of propellants can
be calculated by using Raoult’s law.
Pa = [na/na+nb] POa
o
Pb =[nb/na+nb] P
b
Where Pa and Pb are partial pressures of components
a and b,
na and nb are mole fraction of a and b,
POa
o
and P b are the vapor pressure of pure compound
BLENDS OF CHLOROFLUOROCARBON
PROPELLANTS
PROPELLANT
BLEND
COMPOSITIO VAPOR
N
PRESSURE
(psig) 700F
DENSITY
(g/ml)700F
12/11
12/11
12/114
12/114
12/114
12/114
50:50
60:40
70:30
40:60
45:55
55:45
1.412
1.396
1.368
1.412
1.405
1.390
37.4
44.1
56.1
39.8
42.8
48.4
PROPERTIES OF
CHLOROFLUOROCARBONS (CFC’S)
PROPERTY
TRICHLORO
DICHLORO
MONOFLUORO DIFLUORO
METHANE
METHANE
DICHLORO
TETRA
FLUORO
METHANE
Molecular formula
Numerical
designation
Molecular
weight
Boiling
point(1atm)
Vapor
pressure(psia)
Liquid density
(gm/ml)
CCl3F
CCl2F2
CClF2CClF2
11
12
114
137.28
74.7
23.7
13.4
39.0
1.485
1.403
0.11
120.93
-21.6
-29.8
84.9
196.0
1.325
1.191
0.028
170.93
38.39
3.55
27.6
73.5
1.468
1.360
0.013
Solubility in water
(wt %)
0F
0C
700F
1300C
700C
1300F
770F
CHEMICAL PROPERTIES
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Hydrolysis
Reaction with alcohol- All propellants
except propellants 11 are stable in
presence of alcohol.
Advantages
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Lack of inhalation toxicity
Lack of flammability and explosiveness
High chemical stability except P- 11
High purity
Disadvantages
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Destructive to atmospheric Ozone
Contribute to “greenhouse effect”
High cost
Destruction of Ozone
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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.
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.
Conti…
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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.
Ozone hole in September 2006
“Largest hole in the record.
~Size of North America
September 16 is "World Ozone Day"
Consequences of Ozone depletion
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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.
HYDROCARBONS
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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.
Conti…
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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.
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
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)
C 3H 8
C4H10
C4H10
CH3OCH3
44.1
58.1
58.1
46.1
-43.7
110.0
10.9
30.4
31.1
16.5
-13
63.0
0.50
0.56
0.58
0.66
-156
-117
-101
--
Advantages
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Inexpensive
Minimal ozone depletion
Negligible “greenhouse effect”
Excellent solvents
Non toxic and non reactive
Disadvantages
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Flammable
Aftertaste
Unknown toxicity following inhalation
Low liquid density
HYDROCHLOROFLUOROCARBONS AND
HYDROFLUOROALKANES
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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
Conti..
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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.
PROPERTIES OF
HYDROFLUOROCARBONS (HFC’S)
PROPERTY
TETRAFLUORO
ETHANE
HEPTAFLUORO
PROPANE
Molecular formula
Numerical designation
Molecular weight
CF3CH2F
134a
102
CF3CHFCF3
227
170
-15.0
-26.2
71.1
198.7
1.22
-3.2
-16.5
43 at (200)
--1.41
0.150
Non flammable
0.058
Non flammable
Boiling point(1atm)
0F
0C
Vapor pressure(psia)
Liquid density (gm/ml)
Solubility in water
Flammability
700F
1300C
21.10
% W/W
PROPERTIES OF
HYDROCHLOROFLUOROCARBONS
PROPERTY
DIFLUORO
ETHANE
Molecular formula
Numerical designation
Molecular weight
Boiling point (1 atm)
Liquid density (g/ml)
700F
1300F
700F
CH3CHF2
152a
66.1
-12.0
-11.0
63.0
176.3
0.91
Solubility in water (wt %)
770F
<1.0
Vapor pressure (psia)
0F
0C
Advantages
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Low inhalation toxicity
High chemical stability
High purity
Not ozone depleting
Disadvantages
 Poor solvents
 Minor “greenhouse effect”
 High cost
COMPRESSED GASES
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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 (310 times) and will produce a fairly wet spray and
foams that are not as stable as liquefied gas foams.
Conti..
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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.
PROPERTIES OF COMPRESSED GASES
PROPERTY
CARBON
DIOXIDE
NITROUS
OXIDE
NITROGEN
Molecular formula
Molecular
weight
Boiling point(0F)
CO2
44
N2O
44
N2
28
-109
-127
-320
Vapor pressure
(psia, 700F)
852
735
492
Solubility in water,
770F
0.7
0.5
0.014
1.53
1.53
0.96699
Density (gas) gm/ml
Advantages
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Low inhalation toxicity
High chemical stability
High purity
Inexpensive
No environmental problems
Disadvantages
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Require use of a nonvolatile co-solvent
Produce course droplet sprays
Pressure falls during use
CONCLUSION
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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 CFC’S 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.
References
1) Ansel’s, “ pharmaceutical dosage forms
and drug delivery systems”, 8th edition
2) Remington , " The science and practice of
pharmacy “ , 21st edition
3) Leon. Lachman, “The Theory and Practice
of Industrial Pharmacy”, 3rd edition
4) Gilbert S.Banker, “ pharmaceutical
dosage forms” disperse systems; volume
2; 2nd edition
5) Bentley, “ Text book of pharmaceutics”,
8th edition
6) “Indian Pharmacopoeia”, 2007, Vol-2
7) www.sciencedirectory.com
8) www.wikipedia.com
9) www.appspharmaceutica.com