`
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`
`
`
`TECHNICAL DATA SHEET
`TDS-730
`Edition: August 13, 2010
`Original Date: November 24, 2009 / January 27, 2010
`
`
`Viscosity of Carbopol®* Polymers in
`Aqueous Systems
`
`Introduction
`Carbopol® polymers can be used to develop semisolid and oral liquid formulations with a wide range of flow
`and rheological properties (Figure 1). The polymers are highly efficient thickeners, suspending agents and
`stabilizers at low usage levels (0.1 - 3.0 wt%).
`
`Figure 1: Flow Properties of Carbopol® Polymers, Neutralized Dispersions
`
`
`
`
`
`
`
`
`Low
`Long (Pourable)
`
`Polymer Crosslink Density: High/Medium
` Short
`Flow Property:
`
`
`All Carbopol® polymers are high molecular weight, crosslinked polyacrylic acid polymers. The main
`differences among the polymers are the crosslinker type and density and solvent used to synthesize the
`polymer. A description of the polymers featured in this document is shown in Tables 1A and 1B. Please
`refer to Bulletin 1- Polymers for Pharmaceutical Applications for a complete list of polymers.
`
`
`Table 1A: Carbopol® Polymers Overview
`
`Carbopol®
`Polymer Type Crosslink
`Polymerization
`Recommended
`Density
`Solvent
`Applications
`Polymer
`Homopolymer
`Low
`Ethyl Acetate
`Oral / Topical
`971P NF
`Homopolymer
`Medium
`Ethyl Acetate
`Oral / Topical
`974P NF
`Cosolvent1
`Homopolymer
`High
`Topical
`980 NF
`Homopolymer
`Medium
`Cosolvent
`Topical
`5984 EP
`Interpolymer
`Medium
`Cosolvent
`Topical
`ETD 2020 NF
`Interpolymer
`High
`Cosolvent
`Topical
`Ultrez 10 NF
`1 Cosolvent is a mixture of ethyl acetate and cyclohexane.
`
`
`Lubrizol Advanced Materials, Inc. / 9911 Brecksville Road, Cleveland, Ohio 44141-3247 / TEL: 800.379.5389 or 216.447.5000Lubrizol Advanced Materials, Inc. / 9911 Brecksville Road, Cleveland, Ohio 44141-3247 / TEL: 800.379.5389 or 216.447.5000
`
`The information contained herein is believed to be The information contained herein is believed to be
`
`Materials, Inc.’s direct control. THE SELLER MAKES NO Materials, Inc.’s direct control. THE SELLER MAKES NO
`
`equipment used commercially equipment used commercially
`
`in processing in processing
`
`these these
`
`reliable, but no reliable, but no
`
`representations, guarantees or representations, guarantees or
`
`WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WARRANTIES, EXPRESS OR IMPLIED, INCLUDING,
`
`materials, no warranties or guarantees are made as to materials, no warranties or guarantees are made as to
`
`warranties of any kind are made as to its accuracy, warranties of any kind are made as to its accuracy,
`
`BUT NOT LIMITED TO, THE IMPLIED WARRANTIES BUT NOT LIMITED TO, THE IMPLIED WARRANTIES
`
`the suitability of the suitability of
`
`the products the products
`
`
`for for
`the application the application
`
`suitability for particular applications or the results to be suitability for particular applications or the results to be
`
`OF MERCHANTABILITY AND FITNESS FOR A OF MERCHANTABILITY AND FITNESS FOR A
`
`disclosed. disclosed.
`
` Full-scale Full-scale
`
`testing and end product testing and end product
`
`obtained therefrom. The information is based on obtained therefrom. The information is based on
`
`PARTICULAR PURPOSE. Nothing contained herein is PARTICULAR PURPOSE. Nothing contained herein is
`
`performance are the responsibility of the user. Lubrizol performance are the responsibility of the user. Lubrizol
`
`laboratory work with small-scale equipment and does laboratory work with small-scale equipment and does
`
`to be considered as permission, recommendation, nor to be considered as permission, recommendation, nor
`
`Advanced Materials, Inc. shall not be liable for and the Advanced Materials, Inc. shall not be liable for and the
`
`not necessarily not necessarily
`
`indicate end product performance. indicate end product performance.
`
`as an inducement to practice any patented invention as an inducement to practice any patented invention
`
`customer assumes all risk and liability of any use of customer assumes all risk and liability of any use of
`
`Because of the variations in methods, conditions and Because of the variations in methods, conditions and
`
`without permission of the patent owner. without permission of the patent owner.
`
`handling of any material beyond Lubrizol Advanced handling of any material beyond Lubrizol Advanced
`
`
`
`For further information, please visit www.pharma.lubrizol.comFor further information, please visit www.pharma.lubrizol.com
`Lubrizol Advanced Materials, Inc. is a wholly owned subsidiary of The Lubrizol Corporation
`* Trademark owned by The Lubrizol Corporation
`© Copyright 2010 / The Lubrizol Corporation
`
`
`
`
`Aqueous Gel Viscosity
`Low
`Medium - high
`Very high
`Medium - high
`Medium - high
`Very high
`
`
`
`1
`
`AMN1020
`
`

`

`
`
`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 2 of 10
`
`Europe (Ph. Eur.)
`Carbomers
`Carbomers
`Carbomers
`Carbomers
`---
`---
`
`Japan (JPE)1
`Carboxyvinyl Polymer
`Carboxyvinyl Polymer
`Carboxyvinyl Polymer
`Carboxyvinyl Polymer
`---
`---
`
`Table 1B: Compendial Status of Polymers
`
`United States USP/NF*
`Product Trade Name
`Carbopol® 971P NF Polymer
`Carbomer Homopolymer Type A
`Carbopol® 974P NF Polymer
`Carbomer Homopolymer Type B
`Carbopol® 980 NF Polymer
`Carbomer Homopolymer Type C
`Carbopol® 5984 EP Polymer
`Carbomer Homopolymer Type B
`Carbopol® ETD 2020 NF Polymer Carbomer Interpolymer Type B
`Carbopol® Ultrez 10 NF Polymer
`Carbomer Interpolymer Type A
`* USP/NF after 2006
`
`Brookfield Viscosity of Carbopol® Polymer Dispersions
`
`Carbopol® polymers must be neutralized in order to achieve maximum viscosity. Once a neutralizer is
`added to the dispersion, thickening gradually occurs. Maximum viscosity is typically achieved at a pH of
`6.0 - 7.0.
`
`The viscosity of Carbopol® polymers will begin to decrease at a pH of 9.0 and higher. This is caused by the
`presence of excess electrolytes which affect the electrostatic repulsion of the ionized carboxylic groups. In
`order to obtain high viscosity at pH values below 5 and above 9, an increased concentration of Carbopol®
`polymer is recommended. Additionally, use of a low concentration of polymer at low pH values should be
`avoided in an effort to achieve a robust formulation.
`
`Brookfield viscosity measurements were obtained for aqueous dispersions of several Carbopol® polymers
`at concentrations of 0.2 - 2.0 wt. %. The general behavior of each polymer is shown in Figures 2 - 7 based
`on the data for one lot of each polymer. The dispersions were tested as prepared (conventionally
`represented as pH 3.0) or after neutralization with sodium hydroxide solution to pH 4.0 - 7.0. An increase
`in polymer concentration results in an increase in viscosity. In general, a pH plateau is achieved more
`readily with higher concentrations of Carbopol® polymers.
`
`
`Figure 2: Effect of pH and Concentration on the Viscosity of Carbopol® 971P NF Polymer Dispersion
`
`
`0.2% 971P NF
`0.5% 971P NF
`1.0% 971P NF
`2.0% 971P NF
`
`15000
`
`12000
`
`9000
`
`6000
`
`3000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`
`1 Based on customer request, Lubrizol certifies select lots of product against the JPE Carboxyvinyl Polymer Monograph
`
`
`
`2
`
`

`

`
`Figure 3: Effect of pH and Concentration on the Viscosity of Carbopol® 974P NF Polymer Dispersion
`
`
`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 3 of 10
`
`0.2% 974P NF
`0.5% 974P NF
`1.0% 974P NF
`2.0% 974P NF
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`
`
`
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`Figure 4: Effect of pH and Concentration on the Viscosity of Carbopol® 980 NF Polymer Dispersion
`
`
`0.2% 980 NF
`0.5% 980 NF
`1.0% 980 NF
`2.0% 980 NF
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`
`3
`
`

`

`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 4 of 10
`
`
`
`Figure 5: Effect of pH and Concentration on the Viscosity of Carbopol® 5984 EP Polymer Dispersion
`
`
`0.2% 5984 EP
`0.5% 5984 EP
`1.0% 5984 EP
`2.0% 5984 EP
`
`75000
`
`60000
`
`45000
`
`30000
`
`15000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`
`
`
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`Figure 6: Effect of pH and Concentration on the Viscosity of Carbopol® ETD 2020 NF Polymer Dispersion
`
`
`0.2% ETD 2020 NF
`0.5% ETD 2020 NF
`1.0% ETD 2020 NF
`2.0% ETD 2020 NF
`
`120000
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`
`4
`
`

`

`
`Figure 7: Effect of pH and Concentration on the Viscosity of Carbopol® Ultrez 10 NF Polymer Dispersion
`
`
`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 5 of 10
`
`0.2% Ultrez 10 NF
`0.5% Ultrez 10 NF
`1.0% Ultrez 10 NF
`2.0% Ultrez 10 NF
`
`120000
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`A comparison of the viscosity of 1.0 wt. % aqueous dispersions of several topical grades of Carbopol®
`polymers is shown in Figure 8.
`
`
`Figure 8: Effect of Polymer Type on the Viscosity of 1.0% Dispersions – Topical Products
`
`
`1.0% 980 NF
`1.0% Ultrez 10 NF
`1.0% ETD 2020 NF
`1.0% 5984 EP
`
`75000
`
`60000
`
`45000
`
`30000
`
`15000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`5
`
`

`

`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 6 of 10
`
`
`The effect of polymer type and concentration on the viscosity at pH 6.0 is represented in Figure 9 for
`several topical grades of Carbopol® polymers.
`
`Figure 9: Effect of Polymer Type and Concentration on the Viscosity at pH 6.0 – Topical Products
`
`
`980 NF
`Ultrez 10 NF
`ETD 2020 NF
`5984 EP
`
`120000
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`0
`
`0.5
`
`1.5
`1
`concentration (%)
`
`2
`
`2.5
`
`
`
`A comparison of the viscosity of oral grade Carbopol® 971P NF and 974P NF polymers at various pH levels
`and concentrations is shown in Figure 10.
`
`
`Figure 10: Effect of pH and Concentration on the Viscosity of Carbopol® 971P NF and 974P NF Polymer Dispersions
`
`0.2% 971P NF
`0.5% 971P NF
`1.0% 971P NF
`2.0% 971P NF
`0.2% 974P NF
`0.5% 974P NF
`1.0% 974P NF
`2.0% 974P NF
`
`100000
`
`80000
`
`60000
`
`40000
`
`20000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`6
`
`

`

`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 7 of 10
`
`
`Unneutralized dispersions as prepared have an approximate pH range of 2.5 - 3.5 depending on the
`polymer concentration. The unneutralized dispersions have very low viscosities as shown in Figure 11,
`especially for Carbopol® Ultrez 10 NF polymer and Carbopol® ETD 2020 NF polymers.
`
`Carbopol® Ultrez 10 NF polymer and Carbopol® ETD 2020 NF polymers provide excellent versatility in
`processing for topical formulations. Their unique dispersion performance allows the polymers 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 and ETD
`polymers provide dispersions in water that are much lower in viscosity prior to neutralization which enables
`easier handling in mixing tanks and process lines. Once the polymers are neutralized, they are highly
`efficient thickeners.
`
`Figure 11: Effect of Polymer Type and Concentration on the Viscosity of Dispersions as Prepared
`
`
`971P NF
`974P NF
`980 NF
`Ultrez 10 NF
`ETD 2020 NF
`5984 EP
`
`7500
`
`6000
`
`4500
`
`3000
`
`1500
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`0
`
`0.5
`
`1.5
`1
`concentration (%)
`
`2
`
`2.5
`
`
`In aqueous systems, inorganic bases, such as sodium hydroxide or potassium hydroxide, or low molecular
`weight amines and alkanolamines will provide satisfactory neutralization. Figure 12 shows similar
`thickening efficiencies when sodium hydroxide and triethanolamine are used to neutralize a 0.5 wt%
`aqueous dispersion of Carbopol® 980 NF polymer. No significant differences are expected if potassium
`hydroxide is used for neutralization.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`7
`
`

`

`
`Figure 12: Effect of Neutralizer Type on the Viscosity of 0.5% Carbopol® 980 NF Dispersion
`
`
`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 8 of 10
`
`Sodium hydroxide (18%)
`Triethanolamine (99%)
`
`50000
`
`40000
`
`30000
`
`20000
`
`10000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`2
`
`3
`
`4
`
`5
`pH
`
`6
`
`7
`
`8
`
`
`
`Electrolytes tend to reduce the viscosity of Carbopol® polymer based gels. Therefore, a higher
`concentration of polymer should be used to minimize the viscosity loss. In general, the viscosity of lightly
`crosslinked Carbopol® polymer systems is less affected by electrolytes than highly crosslinked Carbopol®
`polymers. (Figure 13).
`
`
`Figure 13: Effect of Salt on the Viscosity of 1.0% Carbopol® 971P NF and 974P NF Polymer Dispersions at pH 6.0
`
`
`971P NF
`974P NF
`
`75000
`
`60000
`
`45000
`
`30000
`
`15000
`
`Brookfield viscosity @ 20 rpm (mPa*s)
`
`0
`
`0
`
`0.25
`
`0.5
`
`0.75
`% NaCl
`
`1
`
`1.25
`
`1.5
`
`
`
`
`
`8
`
`

`

`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 9 of 10
`
`
`Brookfield Yield Value of Carbopol® Polymer Dispersions
`
`Carbopol® polymers are unique in that they provide a wide range of viscosity profiles and have very high
`yield values, even at low concentrations. These combined features enable the formulation of oral or topical
`suspensions that are stable with low levels of polymer.
`
`Yield value is more important than viscosity when determining suspending ability of a vehicle. While
`viscosity can only slow down the rate of sedimentation, a high yield value is necessary to create permanent
`suspensions.
`
`While all Carbopol® polymers are efficient suspending agents, medium/highly crosslinked polymers have
`higher yield value than lightly crosslinked polymers such as Carbopol® 971P NF polymer (Figure 14).
`Refer to TDS-244 to calculate a theoretical yield value for a suspension.
`
`Figure 14: Effect of Polymer Type on the Brookfield Yield Value of Carbopol® Polymer Dispersions at pH 6.0
`
`
`971P NF
`974P NF
`980 NF
`Ultrez 10 NF
`ETD 2020 NF
`5984 EP
`
`20000
`
`15000
`
`10000
`
`5000
`
`Brookfield yield value (dynes/cm2)
`
`0
`
`0
`
`0.5
`
`1.5
`1
`concentration (%)
`
`2
`
`2.5
`
`
`
`The data included represents one lot of each polymer in an aqueous system. The performance of the
`polymers in other conditions (alternative vehicles, coexcipients and active pharmaceutical ingredients)
`might be different. It is recommended that key performance properties be ascertained and regulatory
`considerations be taken into account in the process of formulation development.
`
`Carbopol® polymers have been used in a variety of commercial liquid and semisolid formulations containing
`the active pharmaceutical ingredients (APIs) noted in Table 2. These APIs have been incorporated in a
`variety of dosage forms: solutions, suspensions, emulsions, lotions, creams, gels and toothpaste for
`peroral or topical administration (skin, mucosa - oral, ophthalmic, nasal, rectal, vaginal).
`
`
`
`9
`
`

`

`TDS-730
`Viscosity of Carbopol® Polymers in Aqueous Systems
`Page 10 of 10
`
`Table 2: Commercial Liquid and Semisolid Formulations Containing Carbopol® Polymers
`
`
`
`
`
`(cid:122)(cid:122) Adapalene
`(cid:122)(cid:122) Aescin
`(cid:122)(cid:122) Allantoin
`(cid:122)(cid:122) Amorolfine hydrochloride
`(cid:122)(cid:122) Azelaic acid
`(cid:122)(cid:122) Benzocaine
`(cid:122)(cid:122) Benzoyl peroxide
`(cid:122)(cid:122) Betamethasone dipropionate
`(cid:122)(cid:122) Betaxolol hydrochloride
`(cid:122)(cid:122) Brinzolamide
`(cid:122)(cid:122) Ciclopirox
`(cid:122)(cid:122) Clarithromycin
`(cid:122)(cid:122) Clindamycin
`(cid:122)(cid:122) Clobetasol propionate
`(cid:122)(cid:122) Clocortolone pivalate/ hexanoate
`(cid:122)(cid:122) Clotrimazole
`(cid:122)(cid:122) Crotamiton
`(cid:122)(cid:122) Cyclosporine
`(cid:122)(cid:122) Dexamethasone
`(cid:122)(cid:122) Dexpanthenol
`(cid:122)(cid:122) Domperidone
`(cid:122)(cid:122) Diclofenac
`(cid:122)(cid:122) Diethylamin-Salicylate
`(cid:122)(cid:122) Estradiol
`
`(cid:122)(cid:122) Estriol
`(cid:122)(cid:122) Etofenamate
`(cid:122)(cid:122) Eucalyptus oil
`(cid:122)(cid:122) Extracts (Capsicum, Arnica)
`(cid:122)(cid:122) Fluocinonide
`(cid:122)(cid:122) Fluorouracil
`(cid:122)(cid:122) Fusidic acid
`(cid:122)(cid:122) Ganciclovir
`(cid:122)(cid:122) Glycerin
`(cid:122)(cid:122) Heparin sodium
`(cid:122)(cid:122) Hydrocortisone
`(cid:122)(cid:122) Hydroquinone
`(cid:122)(cid:122) Hydroxyethylsalicylate
`(cid:122)(cid:122) Ichthammol
`(cid:122)(cid:122) Indomethacin
`(cid:122)(cid:122) Isotretinoin
`(cid:122)(cid:122) Ketoconazole
`(cid:122)(cid:122) Ketoprofen
`(cid:122)(cid:122) Lidocaine
`(cid:122)(cid:122) Menthol
`(cid:122)(cid:122) Mesalamine
`(cid:122)(cid:122) Methyl salicylate
`(cid:122)(cid:122) Metronidazole
`(cid:122)(cid:122) Miconazole nitrate
`
`(cid:122)(cid:122) Naftifine hydrochloride
`(cid:122)(cid:122) Nepafenac
`(cid:122)(cid:122) Nevirapine
`(cid:122)(cid:122) Nonoxynol 9
`(cid:122)(cid:122) Nystatin
`(cid:122)(cid:122) Octyl methoxycinnamate
`(cid:122)(cid:122) Permethrin
`(cid:122)(cid:122) Polidocanol)
`(cid:122)(cid:122) Prilocaine
`(cid:122)(cid:122) Progesterone
`(cid:122)(cid:122) Retinol palmitate
`(cid:122)(cid:122) Rimexolone
`(cid:122)(cid:122) Simethicone
`(cid:122)(cid:122) Sodium alginate
`(cid:122)(cid:122) Sodium fluoride
`(cid:122)(cid:122) Sodium hyaluronate
`(cid:122)(cid:122) Testosterone
`(cid:122)(cid:122) Thioridazine
`(cid:122)(cid:122) Timolol maleate
`(cid:122)(cid:122) Tretinoin
`(cid:122)(cid:122) Tyrothricin
`(cid:122)(cid:122) Urea
`
`
`
`
`
`
`
`10
`
`