Carbopol Polymers: A Versatile Polymer for Pharmaceutical Applications.

 

Prabhakar Panzade* and Prashant K. Puranik

Government College of Pharmacy, Vedant Road, Osmanpura, Aurangabad-431005

*Corresponding Author E-mail: prabhakarpanzade@gmail.com

 

ABSTRACT:

In the recent decades, there has been considerable interest in using Carbopol as an excipient in a diverse range of pharmaceutical applications. Carbopol polymers are polymers of acrylic acid cross-linked with polyalkenyl ethers or divinyl glycol. The Carbopol polymer family is based on cross linked acrylic acid chemistry. The products are cross linked at different levels providing a portfolio of functionally diverse performance options. Carbopol polymers are efficient and effective rheology modifiers. They provide excellent thickening, suspension and stabilization benefits.

 

KEYWORDS: Carbopol, rheology modifier

 


INTRODUCTION:

Carbopol polymers are high molecular weight, cross linked, acrylic acid based polymer. These are polymers of acrylic acid cross-linked with polyalkenyl ethers or divinyl glycol. They are produced from primary polymer particles of about 0.2 to 6.0 micron average diameter. The flocculated agglomerates cannot be broken into the ultimate particles when produced. Each particle can be viewed as a network structure of polymer chains interconnected via cross-linking1.

 

Carbopol polymers were first described in scientific literature back in 1955. Carbomer were first prepared and patented in 19572. Since then, a number of extended release tablet formulations, which involve carbomer matrices, have been patented3. Today, Carbopol polymers are widely accepted ingredients in pharmaceutical dosage systems of almost every form, from controlled release tablets to oral suspensions to other Novel Delivery Systems, as well as a variety of topical products. Although these polymers are very mild acids - weaker than acetic acid - they readily react with alkali to form salts. Aqueous dispersions of Carbopol polymers have an approximate pH range of 2.8 to 3.2 depending on polymer concentration. Greater the concentration, the higher the carboxyl concentration and, therefore, lower the pH. Carbomer readily absorb water, get hydrated and swell. In addition to its hydrophilic nature, its cross-linked structure and it’s essentially insolubility in water makes Carbopol a potential candidate for use in controlled release drug delivery system.

 

STRUCTURE OF CARBOPOL:

Carbopol polymers are offered as fluffy, white, dry powders (100% effective).The carboxyl groups provided by the acrylic acid backbone of the polymer are responsible for many of the product benefits. Carbopol polymers have an average equivalent weight of 76 per carboxyl group. The general structure can be illustrated with fig. No.1 and fig. No. 2

 

CARBOPOL MANUFACTURING AND GRADING:

Carbfopol polymers are manufactured by cross-linking process. Depending upon the degree of cross-linking and manufacturing conditions, various grades of Carbopol are available. Each grade is having its significance for its usefulness in pharmaceutical dosage forms4. Carbopol 934 P is cross-linked with allyl sucrose and is polymerized in solvent benzene. Carbopol 71G, 971 P, 974 P are cross-linked with allyl pentaerythritol and polymerized in ethyl acetate. Polycarbophil is cross-linked polymer in divinyl glycol and polymerized in solvent benzene. All the polymers fabricated in ethyl acetate are neutralized by 1-3% potassium hydroxide. Though Carbopol 971 P and Carbopol 974 P are manufactured by same process under similar conditions, the difference in them is that Carbopol 971 P has slightly lower level of cross-linking agent than Carbopol 974 P. Carbopol 71 G is the granular form Carbopol grade5.

 

MECHANISMS:

A molecule of these polymers in the dry powder state is tightly coiled, thus limiting its thickening capability. When dispersed in water, the molecule begins to hydrate and uncoil slightly, generating an increase in viscosity. However, to achieve the highest possible performance with the polymer, the molecule must be completely uncoiled. There are two mechanisms by which the molecule can become completely uncoiled, providing maximum thickening, emulsion formation and stabilization, or bioadhesion performance. The most commonly used mechanism is accomplished by neutralizing the polymer with a suitable base. Neutralization ionizes the Carbopol polymer, generating negative charges along the polymer backbone. Repulsions of the like negative charges cause the molecule to completely uncoil into an extended structure. This reaction is rapid and results in efficient performance. This is readily done with sodium or potassium hydroxide or amine bases such as Tris (tris (hydroxymethyl) aminomethane). Less polar or non polar solvent systems should be neutralized only with amines.

 

Figure1: General structure of Carbopol polymers

 

Figure2: Schematic drawing of a molecular segment of a cross-linked polyacrylic acid polymer

 

A second thickening mechanism involves the use of a hydroxyl donor. The combination of a carboxyl group and one or more hydroxyl donors will result in thickening because of the formation of hydrogen bonds. This mechanism is time dependent and can take from five minutes to several hours to attain maximum thickening. The pH of such systems will tend to be acidic. Some commonly used hydroxyl donors are polyols (glycerine, propylene glycol, PEGs etc.), sugar alcohols (mannitol, sorbitol etc.), non-ionic surfactants with 5 or more ethoxy groups and others.

 

PHYSICAL PROPERTIES:

The three dimensional nature of these polymers confers some unique characteristics, such as biological inertness, not found in similar linear polymers. The Carbopol resins are hydrophilic substances that are not soluble in water. Rather, these polymers swell when dispersed in water forming a colloidal, mucilage-like dispersion.

 

Carbopol polymers are bearing very good water sorption property. They swell in water up to 1000 times their original volume and 10 times their original diameter to form a gel when exposed to a pH environment above 4.0 to 6.0. Because the pKa of these polymers is 6.0 to 0.5, the carboxylate moiety on the polymer backbone ionizes, resulting in repulsion between the native charges, which adds to the swelling of the polymer. The glass transition temperature of Carbopol polymers is 105°C (221°F) in powder form. However, glass transition temperature decreases significantly as the polymer comes into contact of water. This leads to swelling of the polymer6.

Physical and Chemical Properties of Carbopol polymers are shown in table no.17

 

Table No. 1 Physical and Chemical Properties of Carbopol

Appearance

Fluffy, white, mildly acidic polymer

Bulk Density

Approximately 208 kg/m3 (13 lbs. ft3) *

Specific gravity

1.41

Moisture content

2.0% maximum

Equilibrium moisture content

8-10% (at 50% relative humidity)

PKa

6.0 ± 0.5

pH of 1.0% water dispersion

2.5 - 3.0

pH of 0.5% water dispersion

2.7 - 3.5

Equivalent weight

76 ± 4

Ash content

0.009 ppm (average) **

Glass transition temperature

100-105C (212-221F)

 

RHEOLOGICAL PROPERTIES:

The different grades of Carbopol polymers have different rheological properties, a reflection of particle size, molecular weight between crosslinks and the fraction of the total units, which occur as a terminal, free chain ends. Viscosity range of different carbopol polymers are shown in table no.28,9

Table No. 2 Viscosity Range of Different Carbopol Polymers

No.

Polymer

Viscosity

1

Carbopol 934 NF

30500 – 39400

9

Carbopol 934 P NF

29400 – 39400

12

Carbopol 71 G NF

4000 – 11000

 

APPLICATIONS OF CARBOPOL POLYMERS:

The readily water swellable carbopol polymers are used in a diverse range of pharmaceutical applications to provide Controlled release in tablets, Bioadhesion in buccal, ophthalmic, intestinal, nasal, vaginal and rectal applications.10 Thickening at very low concentrations to produce a wide range of viscosities and flow properties in topical, lotions, creams and gels, oral suspensions and transdermal gel reservoirs. Several properties of Carbopol make it potentially valuable as a pharmaceutical excipient in numerous applications such as:

Controlled release and solid dosage forms:

Carbopol is being used in the controlled release solid dosage formulations since last four decades. The numbers of manufacturers commercializing controlled release tablets using Carbomers are increasing considerably in recent period of development. Tablet formulations using Carbopol polymers have demonstrated zero-order and near zero-order release kinetics. These polymers are effective at low concentrations (less than 10%). Still they show extremely rapid and efficient swelling characteristics in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The Carbopol polymers produce tablets of excellent hardness and low friability. These polymers can be successfully formulated into a variety of different tablet forms, including the traditional swallowable tablets, chewable tablets, buccal tablets, sublingual tablets, effervescent tablets, and suppositories; providing controlled-release properties as well as good binding characteristics.

 

Carbomers show larger dissolution times at lower concentrations than other excipients. Because of these factors Carbopol polymers have greater extent in formulating dosage forms. Because Carbopol polymers swell rapidly in water and absorb great quantities, to avoid the use of flammable solvents, roller compaction is beingused as the method to prepare a new form of Carbopol polymer 71G NF. Carbopol polymer 71G NF is a useful and versatile controlled-release additive for tablet formulations in direct compression11,12

 

In this way carbomers acts as efficient controlled release agents for matrix tablet and also improve bioavailability of certain drugs. They act as efficient binders in dry as well as wet granulation processes as only granular polymer (Carbopol 71G NF) available for direct compression formulation.

 

Oral Suspension Applications:

For many years, Carbopol polymers have been widely used in oral suspensions to thicken, modify flow properties, suspend insoluble ingredients and provide bioadhesion. The significance of these polymers is that they eliminate the settling problem even at low concentrations. As Carbopol polymers swell when hydrated and neutralized, they form colloidal dispersion. They are highly efficient at low level and provide long term stability of suspension over wide pH range. Also they can be used to build viscosity and to mask the bitter taste of certain drugs13,14

 

Bioadhesive Applications:

Many hydrophilic polymers adhere to mucosal surfaces as they attract water from the mucus gel layer adherent to the epithelial surface. This is the simplest mechanism of adhesion and has been defined as “adhesion by hydration” Various kinds of adhesive force, e.g. hydrogen bonding between the adherent polymer and the substrate, i.e. mucus, are involved in mucoadhesion at the molecular level15. Carbopol polymers have been demonstrated to create a tenacious bond with the mucus membrane resulting in strong bioadhesion. Many commercial oral and topical products available today and under investigation have been formulated with Carbopol polymers, as they provide numerous benefits in bioadhesive formulations. Along with excellent adhesion forces, they lower the concentration of active ingredient; provide patient compliance with increased bioavailability of certain drugs.

 

Topical applications:

As the carbomer are safe and effective, non-sensitizing and not having any effect on biological activity of drug, they are well suited to aqueous formulations of the topical dosage forms. They provide excellent thickening, suspending, and emulsification properties for topical formulations.

 

Products with a wide range of viscosities and flow properties have been successfully formulated and commercialized. Carbopol polymers are used to permanently suspend the active ingredients in transdermal reservoirs as well as in topical gels and creams16,17

 

Oral Care Applications:

Carbopol polymers impart several desirable characteristics to toothpaste formulations like Viscosity, Yield Value, Low thixotropy and Clarity. Imparting viscosity at very low concentrations to thicken a system is a primary function of the polymers. Suspending abrasives and solid actives is accomplished through the build of yield value at low polymer concentrations. The combination of Carbopol polymers’ ability to build yield value with low thixotropy provides for a clean, non-stringing ribbon of toothpaste. From aesthetic and practical perspectives this means that Carbopol toothpaste formulations are pumpable, leave minimal solids residue on the tube rim, stand up well on the brush, and can be used in clear formulations18,19.

 

Taste Masking Application of Carbopol:

Carbopol polymer is widely used in formulation and development of taste masked of bitter active pharmaceutical ingredients, because more than 50% of the pharmaceutical formulation having a bitter taste and for the patient convince and pediatric patients it require to mask the bitter taste with suitable method. So carbomer-934 and carbomer-970 was used for the taste masking purpose. Carbomer-934: drugs make a complex by kneading and by microencapsulation and after taste evaluation complexes formulated tablets and evaluate it20.

 

REGULATORY STATUS OF CARBOPOL POLYMERS:

Carbopol polymers, Pemulen polymeric emulsifiers, and Noveon polycarbophils as a class have received extensive review and toxicological evaluation. The Noveon polycarbophils and calcium polycarbophils are classified as Category 1 GRAS (Generally Recognized as Safe) materials. Noveon, Inc., has also determined that Carbopol 934, 934P, 971P, and 974P are GRAS when used in vitamin tablets (assumes a use level of our products between 8% and 30% of the tablet mass, with a typical use of 15% to 20%; the average weight of the vitamin tablet is 500 mg based on the information from the Physician’s Desk Reference, 48th Edition, 1994). The toxicity of Carbopol polymers have been summarized by the Cosmetic Ingredient Review Expert Panel in their assessment of the safety of the Carbopol polymers for cosmetic ingredients. This assessment and subsequent toxicology testing have demonstrated a low toxicity and irritation potential.

 

As a result of the intensive testing and the properties offered by the polymers, they have gained wide acceptance in a variety of pharmaceutical, cosmetic, and detergent applications.21

 

CONCLUSION:

In current scenario, carbopol polymers have variety of applications due to their unique properties. Day by day number of research workers engaged in carbopol polymers is increasing. They have become polymer of choice in most of the formulations. In future, their potential as novel and versatile polymer will be more significant.

 

REFERENCES:

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5.       Noveon Company Technical Literature, 2005.

6.       Martindale – The Complete Drug Reference, 33rd Edition 2002; 1499.

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13.     Borodkin P, Woodward L, Li P, Diesner C, Harmandez L, Vadnere M,Lu  MF: A Polymer Carrier System for Taste Masking of Macrolide Antibiotics, Pharm. Res., 1991; 8(6):706-712.

14.     Delgado A, Gallardo V, Parera A, Gonzalez CF: A study of the Electrokinetic and stability properties of Nitrofurontoin suspensions Part –II  : Flocculation and redispersion properties as compared with theoretical interaction energy curves J. Pharm. Sci., 1990; 79(8):709-715.

15.     Anlar S, Capan Y, Hincal A A: Physico-Chemical and Bioadhesive Properties of Polyacrylic Acid Polymers, Pharmazie, 1993;48(4):285-287.

16.     Gumma A: Measurability of the Bioavailability of an Active Principle Applied Topically, Pharm Acta. Helv., 1971;46(12):7306.

17.     Thoma V K, Klimek R: Untersuchungen zur Photoinstabilität von Nifedipin (Investigations on Photoinstability of Nifedipine, Part 3), Pharm Ind., 1991;53(4).

18.     M Pader: Rheological Properties of Cosmetics and Toiletries, Marcel Dekker, New York, Chapter 7, (1993).

19.     M. Pader: “Gel Toothpastes: Genesis”, Cosmetics & Toiletries,1983;98:71-76.

20.     Perez-Marcos B, Gutierrez C, Gomez-Amoza JL, Martinez-Pacheco R, Souto C, Concheiro A. Usefulness of certain varieties of Carbopol in the formulation of hydrophilic furosemide matrices. Int J Pharmaceut. 1991;67(2):113-121.

21.     Berney BM, Deasy PB. Evaluation of Carbopol 934 as a suspending agent for sulfadimidine suspensions. Int J Phar. 1979;3(2-3):73-80.

 

 

 

Received on 11.01.2010       Modified on 13.02.2010

Accepted on 15.03.2010      © RJPT All right reserved

Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 672-675