See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/382696349
Carbomer A comprehensive review
Article · January 2016
CITATIONS
READS
0
1,616
1 author:
Om Sambhaji Shelke
Sinomune Pharmaceutical Co.
20 PUBLICATIONS 66 CITATIONS
SEE PROFILE
All content following this page was uploaded by Om Sambhaji Shelke on 31 July 2024.
The user has requested enhancement of the downloaded file.
REVIEW ARTICLE
Carbomer: A Comprehensive Review
Shelke Om1*, Kulkarni Amol2
Abstract: Carbomers are polymerized form of acrylic acid monomers. It is widely used in pharmaceutical industry. Polymers
has typical properties such as acidity/alkalinity, density, dissociation constant, glass transition temperature, melting point,
particle size, moisture content, solubility and viscosity. Carbomers are dispersed in either aqueous or alcoholic solution to form
uniform dispersion under stirring. Carbomers need to be neutralizing with alkali to form cross linking between polymers.
Swelling of polymers takes place during neutralization. Neutralization increases viscosity of carbomer solution. Carbomers are
sold in market with different brand name. Carbomer has applications in solid, liquid and semi-solid dosage forms. Carbomers
are available in different grades with different combination with other polymers. Carbomers are used as gelling agents or
viscosity modifier in semisolid dosage form or liquid dosage forms. pH of carbomer plays an important role in building viscosity
by altering the crosslinking.
INTRODUCTION
A carbomer is a homopolymer of acrylic acid, which is
cross-linked, or bonded, with any of several polyalcohol
allyl ethers. Carbomers comes as a white powder to white
fluffy powder. Carbomer is a white fluffy powder that's
used in lotions, gels, creams and other cosmetic formulas as
a thickener, stabilizer and emulsifier. Carbomer does not
actually refer to one particular molecule, but is a generic
term for a series of polymers primarily made from acrylic
acid. Best known for its use in the cosmetic industry, it also
has practical applications in medicine and hygiene. Many
agencies consider the various types to be perfectly safe,
although some of the substances used to neutralize their
pH can be problematic. [1]
Acrylic acid polymers are obtained in the form of an
aqueous suspension of disperse solid-polymer particles
when a monomer composition is polymerized with
agitation, the monomer composition consisting of
ethylenically unsaturated water-soluble monomers
comprising at least about 10 weight percent of acrylic acid
and from 0 up to about 90 weight percent of acrylamide
and the monomer composition being dissolved, at a pH
within the range from about 1 to about 4 in a water
solution of a water soluble ammonium, alkali metal,
alkaline earth metal or zinc salt of a strong inorganic acid
wherein such salt is present in amounts sufficient to
precipitate the polymer formed. [2]
There is a group of polymers, the acrylics, which can be
regarded as based on acrylic acid, more formally named
propenoic acid. It also includes compounds derived from
the acid, which include the methyl, ethyl and butyl esters
and propenonitrile (acrylonitrile), all of which form widely
used polymers. [3]
heated catalyst, often a mixture of bismuth(III) and
molybdenum(VI) oxides on silica, at ca 650 K (Unit 2):
Manufacture of Propenoic Acid (Acrylic Acid) [3]
Propenoic acid is manufactured from propene in two steps.
The first stage is the oxidation of propene to propenal
(acrolein). The alkene and air are mixed and passed over a
Carbomer polymers are formed from repeating units of
acrylic acid. The monomer unit is shown above. Carbomers
are synthetic high-molecular-weight polymers of acrylic
acid that are crosslinked with either allyl sucrose or allyl
ethers of pentaerythritol. They contain between 52% and
68% of carboxylic acid (COOH) groups calculated on the
dry basis.
H2C=CH-CH3(g) + O2(g)՜ H2C=CH-CHO(g) + H2O(g)
The second stage occurs when propenal and air are
passed over another catalyst, a mixture of vanadium(V) and
molybdenum(VI) oxides on silica at ca 550 K:
H2C=CH-CHO(g) +1Τ2O2(g)՜ H2C=CH-CO2H(g)
Manufacture of Poly(Propenoic Acid) (Polyacrylic
Acid)[3]
The polymerization of propenoic acid is a free radical
process, using organic peroxide as an initiator. It can be
carried out with the pure monomer (known as bulk
polymerization), but more often it is polymerized in an
aqueous solution or as an emulsion, also in water:
Structural Formula
1Pacific University, Pacific Hills, Airport Road, Pratapnagar Extension,
Debari, Udaipur-313024, Rajasthan, India.
E-mail: om.shelke20@gmail.com
*Corresponding author
FUNCTIONAL CATEGORY
1. Bioadhesive Material
2. Controlled-Release Agent
2CAYMET’s Siddhant College of Pharmacy, Sudumbare, Pune-412109,
Maharashtra, India.
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
1
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
Table 1: Typical Physical Properties of Carbomer Polymers
Parameter
Acidity/alkalinity
Density (bulk)
Density (tapped)
Dissociation constant pKa
Glass transition temperature
Melting point
Specific gravity:
Particle size distribution
The flocculated powder particles average
A granular carbomer particle size
Specification
pH = 2.5–4.0 for a 0.2% w/v aqueous dispersion
pH = 2.5–3.0 for Acrypol 1% w/v aqueous dispersion.
0.2 g/cm3 (powder); 0.4 g/cm3 (granular).
0.3 g/cm3 (powder); 0.4 g/cm3 (granular).
6.0-0.5
100–105°C
Decomposition occurs within 30 minutes at 260°C.
1.41
Primary particles average about 0.2 mm in diameter.
2–7 mm in diameter and cannot be broken down into the primary Particles.
150–425 mm.
Figure 1: Schematic depicting molecule of carbopol® polymer in
coiled state
Figure 2: Diagram depicting molecule of carbopol® polymer in
uncoiled neutralized state
3. Emulsifying Agent
4. Emulsion Stabilizer
5. Rheology Modifier
6. Stabilizing Agent
7. Suspending agent
8. Tablet Binder.
vigorously stirred water, taking care to avoid the formation
of indispersible agglomerates, then neutralized by the
addition of a base. The Carbopol ETD and Ultrez series of
carbomers were introduced to overcome some of the
problems of dispersing the powder into aqueous solvents.
These carbomers wet quickly yet hydrate slowly, while
possessing a lower unneutralized dispersion viscosity.
Agents that may be used to neutralize carbomer polymers
include amino acids, potassium hydroxide, sodium
bicarbonate, sodium hydroxide and organic amines such as
triethanolamine. One gram of carbomer is neutralized by
approximately 0.4 g of sodium hydroxide. During
preparation of the gel, the solution should be agitated
slowly with a broad, Paddle like stirrer to avoid introducing
air bubbles. Neutralized aqueous gels are more viscous at
pH 6–11. The viscosity is considerably reduced at pH
values less than 3 or greater than 12, or in the presence of
strong electrolytes. Gels rapidly lose viscosity on exposure
to ultraviolet light, but this can be minimized by the
addition of a suitable antioxidant.
Kamal Al-Malah [1] had investigated Rheological
Properties of Carbomer Dispersions as function of
carbomer concentration. They found that below 0.45 wt%
of Carbomer content, Carbomer dispersion behave as a
Newtonian fluid, whereas at or above 0.45 wt%, the
dispersions exhibit shearthinning and rheopectic behavior.
The yield stress results are in harmony with the shear
stress- rate experiments that below 0.45 wt%, a zero-yield
stress value was reported and a non-zero value at or above
that point.
Typical Properties [4]
Typical Physical properties of Carbomer polymers are
shown in Table 1.
Moisture Content
Typical water content is up to 2% w/w. However,
carbomers are hygroscopic and typical equilibrium
moisture content at 25°C and 50% relative humidity is 8–
10% w/w. The moisture content of a carbomer does not
affect its thickening efficiency, but an increase in the
moisture content makes the carbomer more difficult to
handle because it is less readily dispersed.
Solubility
Swellable in water and glycerin and, after neutralization, in
ethanol (95%). Carbomers do not dissolve but merely swell
to a remarkable extent, since they are three-dimensionally
crosslinked microgels.
Viscosity (Dynamic) [5, 6]
Carbomers disperse in water to form acidic colloidal
dispersions that, when neutralized, produce highly viscous
gels. Carbomer powders should first be dispersed into
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
2
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
Table 2: Recommended Neutralizers for Hydroalcoholic Systems [8]
Up to % Alcohol
60%
60%
80%
90%
90%
Neutralizer
Triethanolamine
Tris Amino
AMP Ultra PC2000
Neutrol TE
Triisopropanolamine
Table 3: Most Commonly used Neutralization Ratio Chart
Name
CTFA Name
Manufacturer
NaOH (18%)
Ammonia (28%)
KOH (18%)
L-Arginine
AMP®Ultra PC2000
Neutrol® TE
TEA (99%)
Tris Amino® (40%)*
Ethomeen® C-25
Diisopropanol-amine
Triisopropanol-amine
Sodium Hydroxide
Ammonium Hydroxide
Potassium Hydroxide
Arginine
Aminomethyl Propanol
Tetrahydro-xypropyl Ethylenediamine
Triethanolamine
Tromethamine
PEG-15 Cocamine
Diisopropanol-amine
Triisopropanol-amine
Ajinomoto
Dow
BASF
Dow
Akzo
Dow
Dow
Neutralization Ratio Base/
Carbopol® Polymer
2.3/1.0
0.7/1.0
2.7/1.0
4.5/1.0
0.9/1.0
2.3/1.0
1.5/1.0
3.3/1.0
6.2/1.0
1.2/1.0
1.5/1.0
*Note: The 40% solution should be made from Tris Amino crystals from the manufacturer, Do not use the pre-dispersed solution from the
manufacturer as it contains many impurities
NEUTRALIZATION OF CARBOMERS [7-11]
Neutralization is the process of addition of alkali into the
carbomers slurry and formation of cross links between
carbomers or polymers. Cross linking increases with
increasing the concentration of alkali. Desired viscosity is
achieved with the help of specific concentration of alkali
adjusting to specific pH.
Carbomer polymers must be neutralized in order to
achieve maximum viscosity. Unneutralized dispersions
have an approximate pH range of 2.5-3.5 depending on the
polymer concentration. The unneutralized dispersions
have very low viscosities, especially Carbopol ETD and
Carbopol Ultrez polymers. Once a neutralizer is added to
the dispersion, thickening gradually occurs. Optimum
viscosity is typically achieved at a pH of 6.5-7.5. High
viscosities can be achieved in pH ranges of 5.0-9.0.
The most common neutralizers used, the manufacturers
of these neutralizers and the appropriate ratio to use (as
compared to one part of Carbopol or Pemulen polymers) to
achieve exact neutralization at a pH of 7.0. The chart is
based on Carbopol Ultrez 10 polymer, but is applicable to
all Carbopol and Pemulen polymers because they all have
the same equivalent weight of 76±4.
APPLICATIONS IN PHARMACEUTICAL FORMULATION [4,
9-12]
Carbomers are used in liquid or semisolid pharmaceutical
formulations as rheology modifiers. Formulations include
creams, gels, lotions and ointments for use in ophthalmic,
rectal, topical and vaginal preparations. Carbomer grades
with residual benzene content greater than 2 ppm do not
meet the specifications of the PhEur 6.4 monograph.
Carbomers the most widely used excipient for
thickening lotions creams and gels. Carbomers are also
used to modify the Rheology of water-based systems and to
stabilize multi-phase systems such as emulsions and
suspensions. Carbomers polymers have enabled the
formulation of topical pharmaceutical products for fifty
years and are widely used on a global basis.
The performance of the polymer in semisolid products
is maximized when the macromolecule is fully swollen. The
swelling provides rheology modification, suspending
properties and emulsification to the topical formulation.
Polymer swelling can be accomplished in several ways
(neutralization or hydrogen bonding).
Carbopol® polymers, Pemulen™ polymers and Noveon®
polycarbophil, are polymers of acrylic acid, crosslinked
with polyalkenyl ethers or divinyl glycol. Each polymer
particle is a network structure of polymer chains
interconnected by crosslinks. Without the crosslinks, the
primary particle would be a collection of linear polymer
Thickening Mechanisms [9-11]
Polymers as supplied are dry, tightly coiled acidic
molecules. Once dispersed in water, the molecules begin
to hydrate and partially uncoil. The most common way to
achieve maximum thickening from Carbopol and Pemulen
polymers is by converting the acidic Carbopol or Pemulen
polymer to a salt. This is easily achieved by neutralizing
the Carbopol or Pemulen polymer with a common base
such as sodium hydroxide (NaOH) or triethanolamine
(TEA).
Hydroalcoholic Thickening [9-11]
Ethanol and Isopropanol can be thickened with Carbopol
polymers. The critical factor is choosing the correct
neutralizer based on the amount of alcohol that is to be
gelled. If the wrong neutralizer is used, the salt of the
Carbopol polymer will precipitate out because it is no
longer soluble in the hydroalcoholic blend.
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
3
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
Table 4: Polymer Selection Guide for Semisolid Formulations
Application Type
Product
Trade
Residual
Solvent
Lotions
Creams
Pharmacopeia Monograph
Gels
Bioadhesives
Oral
Liquids/
Semisolids
United State
(USP/NF)
Europe
(Ph. Eur.)
Japan
(JPE)1
Carbomers*
Carboxyvinyl
Polymer
Carbomers*
Carboxyvinyl
Polymer
Carbomers*
Carboxyvinyl
Polymer
Carbomers*
Carboxyvinyl
Polymer
Carbomers*
Carboxyvinyl
Polymer
Carbomers*
Carboxyvinyl
Polymer
-
-
-
-
Name
Carbopol® Polymers
Carbomer
Homopolymer
Type A
Carbomer
Homopolymer
Type A
Carbomer
Homopolymer
Type B
Carbomer
Homopolymer
Type C
Carbomer
Homopolymer
Type A
Carbomer
Homopolymer
Type B
Carbomer
Interpolymer
Type B
Carbomer
Interpolymer
Type A
71G NF
Ethyl
Acetate
√
√
√
√
971P NF
Ethyl
Acetate
√
√
√
√
974P NF
Ethyl
√
√
√
√
√
980 NF
Cosolvent
√
√
√
√
-
981 NF
Cosolvent
√
√
√
-
5984 EP
Cosolvent
√
√
√
√
-
ETD
2020 NF
Cosolvent
√
√
√
√
-
Ultrez
10 NF
Cosolvent
√
√
√
√
-
934 NF
Benzene
√
√
√
√
-
Carbomer
-
934P NF
Benzene
√
√
√
√
√
Carbomer
934P
-
940 NF
Benzene
√
√
√
√
-
Carbomer
-
941 NF
Benzene
√
√
√
-
Carbomer
-
1342 NF
Benzene
Pemulen™ Polymers
√
√
√
-
Carbomer
-
Carboxyvinyl
Polymer
Carboxyvinyl
Polymer
Carboxyvinyl
Polymer
Carboxyvinyl
Polymer
-
-
-
-
-
-
-
√
TR-1 NF
Cosolvent
√
√
√
√
-
TR-2 NF
Cosolvent
√
√
√
√
-
√
√
√
√
Noveon® Polycarbophil USP
Ethyl
AA-1 USP
Acetate
Carbomer
Copolymer
Type B
Carbomer
Copolymer
Type A
Polycarbophil
* The Carbomers Monograph in the European Pharmacopeia stipulates that benzene is limited to 2 ppm. 1 Based on customer request, Lubrizol certifies
select lots of product against the JPE Carboxyvinyl Polymer Monograph
chains, intertwined but not chemically bonded. These
polymers swell in water up to 1,000 times their original
volume (and ten times their original diameter) to form gels
when neutralized. Since the pKa of these polymers is 6±0.5,
the carboxylate groups on the polymer backbone ionize,
resulting in electrostatic repulsion between the negative
particles, which extends the molecule, adding to the
swelling of the polymer. Thickening by hydrogen bonding
is recommended in cases where it is not feasible to increase
the pH of the final formulation. [13]
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
Benefits of Carbomers Topical Formulations [12]
1. Long history of safe and effective use in semi-solid
formulations.
2. Demonstrated to have low irritancy and non-sensitizing
properties with repeated usage.
3. Compatibility with most acidic, basic and neutral drugs.
4. Applications across a broad pH range (4.5 - 10.0).
5. Excellent thickening and suspending agents in aqueous,
anhydrous and hydroalcoholic systems. (Typical use
levels in aqueous systems: 0.1 - 1.0% wt.)
4
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
Table 5: Carbopol® Polymer Recommended Substitutes
Benzene Grade
Carbopol® Polymers
Carbopol® 934 NF polymer
Carbopol® 934P NF polymer
Carbopol® 940 NF polymer
Carbopol® 941 NF polymer
Carbopol® 1342 NF polymer
Recommended Non-Benzene Carbopol® or
Pemulen™ Polymers
Carbopol® 5984 EP and Ultrez 10 NF polymers
Carbopol® 974P NF polymer
Carbopol® 980 NF and Ultrez 10 NF polymer
Carbopol® 71G NF, 971P NF and 981 NF polymers
Pemulen™ TR-1 NF and TR-2 polymers
6. Consistent and reproducible properties due to their
synthetic nature.
7. Do not support microbial growth.
8. Chemically stable and maintain formulation stability.
9. Excellent dispersions can be formed without alternate
heating and cooling cycles.
10. No heat sensitivity compared to other thickening agents.
11. Formulations can be sterilized by autoclaving or gamma
radiation.
12. Provide a non-greasy formulation, with no irritation.
13. Function as primary emulsifiers (Pemulen™ polymers)
or emulsification stabilizers (Carbopol® polymers).
14. Possess shear thinning properties to facilitate extrusion
from product packaging.
15. Can increase bioavailability of the active pharmaceutical
ingredient due to their bioadhesive properties.
aids and emulsifying agents for topical formulations and
oral liquids/semisolids. A key benefit of the polymers is
their high efficiency at low usage levels (0.1 - 3 wt. %).
Carbopol® polymers can be used as rheology modifiers in
anhydrous systems with or without neutralization.
Carbopol® Ultrez 10 NF polymers provides excellent
versatility in processing for topical formulations. Its unique
dispersion performance allows it to wet quickly, yet
hydrate slowly. This minimizes agglomeration, which can
be a problem if turbulent mixing is not available during
dispersion. Compared with traditional Carbopol® polymers,
Carbopol® Ultrez 10 NF polymer provides dispersions in
water that are much lower in viscosity prior to
neutralization which enables easier handling in mixing
tanks and process lines. Once the polymer is neutralized, it
is a highly efficient thickener.
According to Mohammad T Islam et al., [15] the
viscoelasticity increases with increasing pH but the change
is not significant. Carbopol microgels shows significant
pseudoplastic flow curves at different temperature. The
enhanced non-Newtonian trends in topical formulations
can be attributed to the increased solvent-Solvent and
polymer-solvent attractions and higher viscosity of cosolvent glycerol. Several rheological techniques confirm
that substantial amounts of stress greater than the yield
values of the topical gels are required before the topical
gels can start to flow. The yield stress values depend on the
method used and range from 28 Pa to 188 Pa. In terms of
strain, the required values to break the gel networks are
within 80±20%. Comparisons of the flow curves were
performed with the simple well-known constitutive models
to determine their applicability. The viscoelastic nature of
Carbopol dispersions with substantial yield strength
suggests that such aqueous gels may be useful as topical
and mucoadhesive delivery systems. The long relaxation
time, remarkable temperature stability and low thixotropy
of the gels make them amenable in delivery systems
requiring prolonged drug residence time with enhanced
absorption at the application areas. The rheological
parameters can be used along with other studies such as
bioavailability and residence time of drugs to construct a
framework for designing optimal drug delivery systems.
Typical usage levels of Carbopol® polymers in topical
aqueous or hydroalcoholic gels is 0.5% - 3 wt. %.
SELECTING THE RIGHT POLYMERS FOR SEMISOLID
APPLICATIONS [12-14]
Numerous enhancements have been made to the Carbopol®
polymer family over time to address regulatory
requirements, meet formulation demands and improve
product handling during processing. For example, the
solvent system used to synthesize the polymers has
evolved. Specifically, the “traditional” polymers are
synthesized in benzene and the “toxicologically preferred”
polymers are synthesized in either ethyl acetate or a
cosolvent mixture of ethyl acetate and cyclohexane.
Additionally, Carbopol® ETD and Ultrez polymers provide
greater versatility in formulating and processing with their
improved ease of dispersion. Table 4 can be used for
general guidance in selecting the appropriate polymer for
semisolid formulations.
CARBOPOL® POLYMER RECOMMENDED SUBSTITUTES
[12-14]
The Table 5 shows recommended substitutes for the
benzene grade Carbopol ® products based on viscosity
criteria. The substitute products are polymerized in either
ethyl acetate or a cosolvent mixture of ethyl acetate and
cyclohexane. If a substitution is made in a pharmaceutical
formulation, it is recommended that key performance
properties be ascertained and regulatory considerations be
taken into account. Depending on the desired dosage
requirements, other Carbopol® polymers may be suitable
alternatives.
General Recommendations for Formulation and
Processing
1. Choice of Neutralizer
Upon neutralization, Carbopol® polymer should form a salt
that is swellable in the vehicle.
FORMULATING TOPICAL GELS [12]
Carbopol® polymers, Pemulen™ polymers and Noveon®
polycarbophil are highly efficient thickeners, suspending
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
5
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
2. pH
The optimum pH range for a Carbopol® polymer is 4 - 10.
Soluble ingredients can be dissolved in the water used to
make the polymeric dispersion. Some soluble ingredients
are added to the final formulation to avoid compatibility
issues (for example, electrolytes are added at the end).
3. Complexation with Other Ingredients
Proteins,
povidone,
polyethylene
glycol
and
polyethoxylated surfactants might form a complex with
unneutralized Carbopol® polymers. In order to prevent the
complexation, these ingredients should be added to the
partially neutralized dispersion.
3. High Shear Mixing or Pumping
Carbopol® polymers thicken by forming a gel matrix. High
shear mixing, with colloid mills, homogenizers, etc., or high
shear pumping can break down the polymer structure
resulting in viscosity loss. If necessary, an in-line
homogenizer can be used to minimize the homogenization
time. Low shear pumps, such as reciprocating diaphragm
or auger/gear pumps should be used.
4. Electrolytes, Metals
Carbopol® polymers are sensitive to electrolytes and
preferably their level should be minimized. It is
recommended to use the non ionized form of the API
whenever possible. An increased level of Carbopol®
polymer may be used to compensate for the effect of
electrolytes on viscosity. Alternatively, a more salt tolerant
grade of the polymer may be used such as Carbopol® ETD
2020 NF, Pemulen™ TR-1 NF or Pemulen™ TR-2 NF
polymers. Additionally, deionized or distilled water should
be used. Salts should be added after neutralization of the
dispersion in order to reduce their impact on product
viscosity. Multivalent cations (Ca2+, Mg2+, Fe3+, Al3+, etc.)
should not be used with Carbopol® polymers.
Contamination with transition metals (Fe, Cu, etc.)
causes a gradual reduction in viscosity. It is recommended
to include EDTA in the formulation as a complexing agent.
Processing in stainless steel or nonmetallic equipment will
minimize the effect of metals.
TRANSPARENT HYDROALCOHOLIC GELS [12, 16, 17, 23]
Ethanol or other alcohols (propylene glycol, isopropanol)
can be used in hydroalcoholic gels to dissolve low solubility
active pharmaceutical ingredients instead of using
solubilizers such as PEG-40 hydrogenated castor oil,
polysorbate 20, etc. The absence of a solubilizer greatly
improves the aesthetics of the product as the stickiness and
“rubbery” feel is virtually absent. Due to the large ethanol
content, additional preservatives may not be required.
The viscosity of an aqueous gel is usually higher than
the viscosity of a hydroalcoholic gel due to more hydrogen
bonding. Viscosity of the hydroalcoholic gel can be adjusted
by increasing the level of Carbopol® polymer.
To manufacture transparent hydroalcoholic gels based
on Carbopol® polymer, the ethanolic solution should be
added to the hydrogel (Carbopol polymer pre-dispersed in
water) using a slowly moving anchor mixer. Also, to reduce
air entrapment in the final product, the ethanol solution
should be degassed prior to addition as the solubility of air
in ethanol is quite high. Degassing of the alcoholic solution
is best done by filtering through a glass filter under
reduced pressure.
Neutralization of hydroalcoholic gels with Carbopol®
polymer can be accomplished using different bases. The
amine salt of Carbopol® polymer must be swellable in the
solvent system. If it is not, it will precipitate and no
thickening will occur. Triethanolamine can be used in
hydroalcoholic gels with up to 50% alcohol. A higher
alcohol level requires more alcohol soluble amines, such as
tetrahydroxypropyl ethylenediamine, PEG 15 Cocamine, diisopropylamine, amino methyl propanol or tromethamine.
Some of the literature has reported that the gel
formulated using carbomers has good drug releasing
capacity. [18-20]
5. Dispersion Techniques
Like many fine powders, traditional Carbopol® polymers,
as well as Pemulen™ polymers and Noveon® polycarbophil,
tend to agglomerate when improperly added to the solvent.
Therefore, proper dispersion techniques must be followed
to prevent excessively long mixing cycles, reduced viscosity
and dispersion defects such as grainy texture, fluctuations
in pH and viscosity and the formation of insoluble particles
resembling “fish eyes.” If improper dispersion techniques are
utilized, the surface of the agglomerated particles solvates
to form a tough outer layer which prevents complete
wetting of the interior polymer particles. Carbopol®
polymers can be dispersed by sifting the polymer into water,
using an eductor or mechanical in-line powder disperser.
Incorporating Active Pharmaceutical Ingredients into
Carbopol® Polymer Dispersions
Carbopol® polymers, Pemulen™ polymers and Noveon®
polycarbophil dispersions can be used as the vehicle in
liquid and semisolid dosage forms. Other pharmaceutical
ingredients are incorporated into the formulation via two
different methods depending on the physical/chemical
properties.
FORMULATING CREAMS AND LOTIONS [12, 21, 24]
Carbopol® polymers can be used to stabilize creams and
lotions. In contrast, Pemulen™ polymers can both stabilize
and emulsify (function as primary emulsifiers) oil-in-water
emulsion. These emulsifiers have a small lipophilic portion
in addition to a large hydrophilic portion. The lipophilic
portion adsorbs at the oil-water interface and the
hydrophilic portion swells in the water forming a gel
network around oil droplets to provide exceptional
emulsion stability to a broad range of oils.
1. Insoluble Ingredients
Insoluble ingredients can be incorporated into the
polymeric dispersion either before or after it is neutralized.
2. Soluble Ingredients
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
6
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
Table 6: Carbopol® Polymer Selector Guide
Carbopol® Polymers
Flow Type
Compatibility
High Electrolytes
Surfactants
Solvents
Chlorine Bleach
Hyrdogen Peroxide †
High pH
(>11)
Low pH (3-4)
674
Long
***
**
**
**
***
Traditional
676
690
Short
Short
**
**
**
**
**
**
***
***
**
**
Enhanced Dispersing
ETD 2623
ETD 2691
Medium
Long
***
***
***
**
***
**
**
**
***
EZ-2
Short
*
*
**
**
Self-Wetting
EZ-3
EZ-4
Short
Medium
**
***
**
***
***
***
**
**
***
***
***
**
***
**
**
**
***
**
-
-
***
-
-
-
***Excellent, **Good, *Fair, † Must use UV absorber and chelating agent for stability
Table 7: Carbopol® Polymers – Properties
Polymer
Flow Characteristics
Suspending Ability
Relative
Viscosity
Short
Long
674
-
√
√
Low
676
√
-
√
High
690
√
-
√
High
ETD 2691
-
√
√
Low
ETD 2623
-
√
√
Medium
EZ-2
√
-
√
High
EZ-3
√
-
√
High
EZ-4
-
√
√
Medium
Aqua 30
-
√
√
Low
FORMULATING TOPICAL EMULSIONS [12, 22-26]
Typical usage levels of Pemulen™ polymers in topical
emulsions is 0.1% - 0.4 wt%. More Pemulen™ polymer is
not necessarily better. The viscosity of the external phase
can be increased by using Carbopol® polymer in addition to
Pemulen™ polymer.
Low surfactants, High pH, Solvents,
High electrolyte
Low surfactants, High pH, Chlorine
bleach, Solvents, High electrolyte
Low surfactants, High pH, Chlorine
bleach, Solvents, High electrolyte
Low surfactants, High pH, Solvents
Low surfactants, High pH, Hydrogen
peroxide, Solvents, High electrolyte
Low surfactants, High pH, Hydrogen
peroxide
Low surfactants, High pH, Solvents,
High electrolyte, Hydroalcoholic
Low surfactants, High pH, Hydrogen
peroxide, Solvents
High surfactants, High pH, Low pH,
Hydrogen peroxide
3. Electrolytes, Metals
Pemulen™ polymers are sensitive to electrolytes and
preferably their level should be minimized. It is
recommended to use the non ionized form of the API
whenever possible. Additionally, deionized or distilled
water should be used. Salts should be added after
neutralization of the dispersion in order to reduce their
impact on product viscosity. Multivalent cations (Ca2+, Mg2+,
Fe3+, Al3+, etc.) should not be used with Pemulen™ polymers
because they will break the emulsion.
Contamination with transition metals (Fe, Cu, etc.)
causes a gradual reduction in viscosity and emulsion
instability. It is recommended to include EDTA in the
formulation as a complexing agent. Processing in stainless
steel or nonmetallic equipment will minimize the effect of
metals.
General recommendations for Formulation and
Processing
1. pH
The optimum pH range for an emulsion using Pemulen™
polymeric emulsifiers is 4-8. A pH above or below this
range may cause an unstable emulsion.
2. High Shear Mixing or Pumping
Pemulen™ polymers stabilize the emulsion by forming a gel
around the oil droplet. High shear mixing, with colloid
mills, homogenizers, etc., or high shear pumping can break
down the polymer structure resulting in viscosity loss and
emulsion instability. If necessary, an in-line homogenizer
can be used to minimize the homogenization time. Low
shear pumps, such as reciprocating diaphragm or
auger/gear pumps should be used. [27]
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
Suitable for Use in Systems
Containing
4. Droplet Size
Pemulen™ polymers can produce extremely stable macro
emulsions, even at large average oil droplet sizes
(approaching 1 - 2 millimeters diameter). For aesthetic
reasons, it is often desirable to produce small particle size
emulsions having a high degree of whiteness, opacity and
7
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in
REVIEW ARTICLE
12. Lubrizol. Formulating Semisolid Products. Pharmaceutical
Bulletin, 21:1-7, 2011.
13. Kadajji V G, Betageri G V. Water Soluble Polymers for
Pharmaceutical Applications. Polymers, 3:1972-2009, 2011.
14. A-sasutjarit R, Sirivat A, Vayumhasuwan P. Viscoelastic
Properties of Carbopol 940 Gels and Their Relationships to
Piroxicam Diffusion Coefficients in Gel Bases. Pharm Res,
22(12):2134-40, 2005.
15. Mohammad IT, Naır RH, Susan C, Chrisita A. Rheological
characterization of topical carbomer gels neutralized to
different pH. Pharmaceutical Research 21(7):1192-99, 2004.
16. Al-Khamis K I, Davis S S, Hadcraft J. Microviscosity and drug
release from topical gel formulations. Pharm. Res 3(4):214-17,
1986.
17. Jimenez M M, Fresno M J, Ramirez A. The influence of
cosolvent polarity on the flow properties of hydroalcoholic
gels: empirical models. Chem Pharm Bull (Tokyo), 53(9):
1097-102, 2005.
18. Mutalik S R, Udupa N. Formulation development, in vitro and
in vivo evaluation of membrane controlled transdermal
systems of glibenclamide. J Pharm Pharmaceut Sci, 8(1):26-38,
2005.
19. Tas C Ozkan Y, Savaşer A, Baykara T. In-vitro and ex-vivo
permeation studies of chlorpheniramine maleate gels
prepared by carbomer derivatives. Drug Dev Ind Pharm,
30:637–47, 2004.
20. Waghmare N, Waghmare P, Wani S, Yerawar A. Development
of Isotretinoin Gel for the Treatment of Acne Vulgaris. RJPBCS,
2(1):220-30, 2011.
21. Cornelia I, Dan FA, Marieta B, Alina I. The Behavior of
Carbopol 980 in Aqueous Solutions Of Nonionic Surfactants. II.
Evidence of Complex Formation by Electrical Conductivity,
Steady-State Fluorescence, Dye Solubilization and Turbidity
Measurements. Revue Roumaine de Chimie, 55(6):341-47
2010.
22. Bremecker K, Koch B, Krause W, Neuenroth L. Applicationtriggered drug release from an oil-in-water emulsion. Pharm
Ind, 54(2):182-5, 1992.
23. DiColo G, Carelli V, Giannaccini B, Serafini M F, Bottari F.
Vehicle effects in percutaneous absorption: in-vitro study of
influence of solvent powder and microscopic viscosity of
vehicle on benzocaine release from suspension hydrogels. J
Pharm Sci, 69(4):387-91, 1980.
24. Fiorilli A, Molteni B, Milani M. Successful treatment of
bacterial vaginosis with a polycarbophil-Carbopol acidic
vaginal gel: results from a randomised double-blind, placebocontrolled trial. Eur J Obstet Gynecol Reprod Biol, 120(2):2025, 2005.
25. Oppong F K, Rubatat L, Friske B J, Bailey A E, Bruyn J R.
Microrheology and structure of a yield-stress polymer gel.
Phys Rev E Stat Nonlin Soft Matter Phys, 73(4–1):041405/1-9,
2006.
26. Lubrizol. Bioadhesion. Pharmaceutical Bulletin, 23:1-20 2011.
27. Schmucker-Castner J, Desai D. Rheology modification of
hydrogen peroxide-based applications using cross-linked
polyacrylic acid polymers. Int J Cosmet Sci, 21(5):313-25,
1999.
creamy appearance. The droplet size of the oil phase can be
reduced by increasing the mixing time, using moderate
shear agitation when the emulsion is made, or by the use of
a liquid nonionic surfactant (HLB 8-12) at 0.1 - 0.4 wt. %.
5. Emulsification Method
Both a direct and indirect method could be used to create
an emulsion with Pemulen™ polymers.
CONCLUSION
Carbomers are synthetic high-molecular-weight polymers
made of Acrylic acid monomers by polymerization process.
Carbomers are used in different formulation as bioadhesive
material, controlled-release agent, emulsifying agent,
emulsion stabilizer, rheology modifier, stabilizing agent,
suspending agent, tablet binder. Carbomer polymers have
typical physical properties. Quality of Carbomer polymers
controlled with the typical physical properties. Hydration
of Carbomer polymers on hydration leads to uncoiling of
polymers. Carbomer polymers need to neutralize for
desired pH to achieve Viscosity. Various types of
Neutralizer used depending on the formulation whether it
is alcoholic or nonalcoholic. Carbomer polymers
incorporated in creams, gels, lotions and ointments for use
in ophthalmic, rectal, topical and vaginal preparations.
Different types of grades of Carbomer polymers are
available depending upon the use such as Carbopol®,
Pemulen™ TR and and Ultrez 10.
REFERENCES
1. Kamal Al-Malah. Rheological Properties of Carbomer
Dispersions. Annual Transactions of the Nordic Rheology
Society, 14:1-9, 2006.
2. Henry V, Bay C, Percy J H, Midland M. Acrylic Acid Polymers.
United States Patent Office, 3, 493, 500, 1970.
3. essentialchemicalindustry.org.
Poly
(propenoic
acid)
(polyacrylic
acid).
Available
from:
http://www.essentialchemicalindustry.org/polymers/polypr
openoic-acid.html.
4. Raymond C R, Paul J S, Marian E Q. Carbomer. Hand book of
Pharmaceutical Excipients, Sixth edition. Pharmaceutical
Press, London, 110-14, 2009.
5. Tamburic S, Craig D Q M. Investigation into the rheological,
dielectric and mucoadhesive properties of poly (acrylic acid)
gel systems. J Control Release, 37:59–68, 1995.
6. Chu J S, Yu D M, Amidon G L, Weiner N D, Goldberg A H.
Viscoelastic Properties of Polyacrylic Acid Gels in Mixed
Solvents. Pharm Res, 9:1659–63, 1992.
7. Chemicaloftheday.squarespace.com.
Today's
Chemical:
Carbomer.
Available
from:
http://chemicaloftheday.squarespace.com/todayschemical/2011/8/31/carbomer.html.
8. Lubrizol. Neutralizing Carbopol® and Pemulen™ Polymers in
aqueous and hydroalcoholic systems. Technical Data Sheet,
237:1-3, 2009.
9. Lubrizol. Formulating Hydroalcoholic Gels with Carbopol®
Polymers. Technical Data Sheet, 255:1-6, 2009.
10. Lubrizol. Viscosity of Carbopol®* Polymers in Aqueous
Systems. Technical Data Sheet, 730:1-10, 2010.
11. Lubrizol. How to Prepare Aqueous Dispersions of Carbopol®
Polymers. Technical Data Sheet, 61:1-2, 2010.
Inventi Rapid: Pharm Tech Vol. 2016, Issue 1
[ISSN 0976-3783]
View publication stats
Cite this article as: Shelke Om, Kulkarni Amol.
Carbomer: A Comprehensive Review. Inventi Rapid:
Pharm Tech, 2016(1):1-8, 2015.
8
2016 ppt 17832 © Inventi Journals (P) Ltd
Published on Web 16/11/2015, www.inventi.in