Carbopol and its Applications in pharmaceutical dosage forms

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Shridhar J Pandya

Shridhar

Carbopol polymers 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 micron average diameter. The flocculated agglomerates cannot be broken down into the ultimate particle when produced.

Each primary particle can be viewed as a network structure of polymer chains interconnected by cross-links. Without the cross-links, the primary particle would be a collection of linear polymer chains intertwined but not chemically bonded. Carbopol polymers, along with Pemulen® and Noveon® polymers are all cross-linked. 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 groups on the polymer backbone ionize, resulting in repulsion between the negative 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, the glass transition temperature decreases significantly as the polymer comes into contact with water. The polymer chains start gyrating, and the radius of gyration becomes increasingly larger. Macroscopically, this phenomenon manifests itself as swelling.

The readily water-swellable Carbopol polymers are used in a diverse range of pharmaceutical applications to provide:

  • Controlled release in tablets. Carbopol polymers offer consistent performance over a wide range of desired parameters (from pH-derived semi-enteric release to near zero-order drug dissolution kinetics) at lower concentrations than competitive systems.
  • Bioadhesion in buccal, ophthalmic, intestinal, nasal, vaginal, and rectal applications. Noveon AA-1 USP polycarbophil is the recognized industry standard for bioadhesion.
  • Thickening at very low concentrations (less than 1%) to produce a wide range of viscosities and flow properties in topical lotions, creams and gels, oral suspensions, and in transdermal gel reservoirs.
  • Permanent suspensions of insoluble ingredients in oral suspensions and topicals.
  • Emulsifying topical oil-in-water systems permanently, even at elevated temperatures, with essentially no need for irritating surfactants.

Oral Suspension Applications of Cabopol

Carbopol polymers have been used worldwide in oral suspensions for many years to thicken, modify flow characteristics, suspend insoluble ingredients, and to provide bioadhesion. These cross-linked polymers of acrylic acid provide excellent suspending ability for insoluble ingredients, and virtually eliminate the problem of settling, even when used at very low levels. Carbopol polymers swell when hydrated and neutralized, forming a colloidal dispersion. The insoluble ingredients in the suspensions are then permanently trapped in the interstitial spaces between the hydrogel particles. 6-7

The original oral Carbopol polymer, 934P NF, has been used in oral suspensions worldwide since the mid 1960s. Carbopol 974P NF polymers have similar rheological properties to Carbopol 934P NF: both are highly cross-linked polymers that produce mucilages with very short flow rheology. Short flow rheology can be characterized as a gelled consistency similar to mayonnaise. Carbopol 971P NF polymers, lightly cross-linked polymers, provide very low viscosities and excellent yield values at low usage levels. Suspensions formed with Carbopol 971P NF polymers will have longer rheology and will flow like honey. Carbopol 71G polymers, a granular form of 971P NF polymers, will give the same viscosity and rheology as 971P NF, but are easier to handle and disperse.

Controlled-Release & Solid Dosage Applications of Carbopol

Although Carbopol polymers have enjoyed success in controlled-release solid dose formulations since the 1960s, the number of companies developing and commercializing controlled-release tablets using Carbopol and Noveon polymers has increased significantly in recent years. In response to this commercial interest, we have tested a variety of excipients and active drug ingredients in tablet models using both direct-compression and wet granulation methods. 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.

Tablet formulations using Carbopol polymers have demonstrated zero-order and near zero-order release kinetics. 1-5 These polymers are effective at low concentrations (less than 10%) and feature extremely rapid and efficient gelation characteristics under both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) test conditions. They also produce tablets of excellent hardness and low friability over a range of compression forces, as well as demonstrably longer dissolution times at lower concentrations than other controlled-release excipients. Greater formulating latitude in dosage forms is therefore possible using Carbopol polymers as the functional controlled-release excipient.

Because Carbopol polymers swell rapidly in water and absorb great quantities, to avoid the use of flammable solvents, we use roller compaction as the method to prepare a new form of Carbopol polymer 71G NF. It is compressed into tapes, which are fed into a mill where the particle size is reduced to the desired range and has the following typical properties:

  • Flo-Dex (mm) 6-12
  • Loose Bulk Density (g/cm 3 ) 0.39-0.45
  • Tap Density (g/cm 3 ) 0.47-0.56
  • BET Surface Area (m 2 /g) 10-12

Carbopol polymer 71G NF is a useful and versatile controlled-release additive for tablet formulations in direct compression with the following characteristics:

  • Good tableting formulation flowability,
  • Good tablet hardness with press-operating latitude,
  • Good tablet friability over variations in press speed and compression pressure,
  • Long drug release profiles (often zero order),
  • Release profiles can be controlled by varying Carbopol 71G NF polymer levels,
  • Can be processed by wet granulation if desired, and
  • Can give Drug Release Profiles similar to Carbopol 971P NF polymer, but with less dust and better handling characteristics.

Bioadhesive Applications of Cabopol

Bioadhesion (or mucoadhesion) is generally understood to define the ability of a biological or synthetic material to “stick” to a mucous membrane, resulting in adhesion of the material to the tissue for a protracted period of time. This concept has received a significant degree of attention due to potential applications in drug delivery and enhanced drug bioavailability, which results from the lengthened period of time in which the bioadhesive dosage form is in contact with the absorbing tissue versus a standard dosage form.

Many commercial oral and topical products available today have been formulated with Carbopol and Noveon polymers, as they have numerous features that provide key benefits in bioadhesive formulations. 2-4 Carbopol and Noveon polymers:

  • Are safe and effective in oral and topical applications,
  • Are bioadhesive, enabling increased bioavailability of ophthalmic, nasal, buccal, intestinal, rectal, and vaginal formulations,
  • May protect proteins and peptides from degradation by proteolytic enzymes, enabling increased bioavailability of protein- or peptide-based formulations, and
  • Are approved by many of the world’s pharmacopoeias, facilitating regulatory approvals worldwide.

Topical Applications of Cabopol

Carbopol, Pemulen, and Noveon polymers are very well suited to aqueous formulations of the topical dosage forms. Many commercial topical products available today have been formulated with these polymers, as they provide the following numerous benefits to topical formulations:

  • Safe & Effective — Carbopol, Pemulen, and Noveon polymers have a long history of safe and effective use in topical gels, creams, lotions, and ointments. They are also supported by extensive toxicology studies.
  • Non-Sensitizing — Carbopol, Pemulen, and Noveon polymers have been shown to have extremely low irritancy properties and are non-sensitizing with repeat usage.
  • No Effect on the Biological Activity of the Drug — Carbopol polymers provide an excellent vehicle for drug delivery. Due to their extremely high molecular weight, they cannot penetrate the skin or affect the activity of the drug.
  • Excellent Thickening, Suspending, & 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 creams. Pemulen polymeric emulsifiers can be used to prepare stable emulsions, such as turpentine liniment, without the use of surfactants. Carbopol polymers and Pemulen polymeric emulsifiers are often the thickener and emulsifier of choice in topical lotions.

Taste Masking Application 4 of Carbopol

Carbopol polymer is widely used in formulation & 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 & carbomer-970 was used for the taste masking purpose. Carbomer-934: drugs make a complex by kneading and by microencapsulation & after taste evaluation complexes formulated tablets and evaluate it.

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. 6 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

Chewable dosage forms of Carbopol

Disclosed is a soft, chewable dosage form, including a matrix of hydrogenated starch hydrolysate, a water soluble bulking agent, and a water insoluble bulking agent. The present invention also includes a method of preparing a soft, chewable dosage form, including the steps of mixing under high shear force, a hydrogenated starch hydrolysate, a water soluble bulking agent, and a water insoluble bulking agent until a uniformly blended matrix is obtained. Active ingredients may optionally be incorporated in the matrix.

Physical Properties 5

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. The polymer chains start gyrating and radius of gyration becomes increasingly larger. Macroscopically, this phenomenon manifests itself as swelling.

Table No.1 Physical and Chemical Properties of Carbopol 6

Appearance

Fluffy, white, mildly acidic polymer

Bulk Density

Approximately 208 kg/m 3 (13 lbs. ft 3 ) *

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

100-105 0 C (212-221 0 F)

* Polymers produced in co solvent (a cyclohexane / ethyl acetate mixture) have a bulk density of 176 kg/m 3 (11 lbs/ft 3 ).

* * Polymers produced in ethyl acetate have ash content (as potassium sulfate) of 1-3% on average.

References:

  1. Florence AT, Jani Pu. Novel oral drug formulations. their potential in modulating adverse-effects. Drug Saf. 1994;410(3):233-266.
  2. Choulis , NH , Papadopoulos H, Choulis M. Long-acting methadone. Pharmazie. 1976;31:H.7.
  3. Durrani, Manzer J, Whitaker R, Benner SC. A comparative study of controlled release agents, part I: effects of compression force and polymer concentration. Abstract in Volume No. 19 presented at the Annual Meeting of the American Association of Pharmaceutical Scientists;1992.
  4. 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.
  5. Perez-Marcos B, Iglesias R, Gomez-Amoxa JL. Mechanical and drug release properties of atenolol-Carbopol hydrophilic matrix tablets. J Controlled Rel. 1991;17(3):267-276.
  6. Berney BM, Deasy PB. Evaluation of Carbopol 934 as a suspending agent for sulfadimidine suspensions. Int J Phar. 1979;3(2-3):73-80.
  7. Borodkin P, Woodward L, Li P, Diesner C, Harnandez L, Vadnere M, Lu MF. A polymer carrier system for taste masking of macroglide antibiotics. Pharma Res. 1991;8(6):706-712.

About Authors:

Shridhar J Pandya * , D Harinarayana, Devendra. K. Jain, Shital. J. Bidkar, Jatin Patel.

Department of pharmaceutics , AISSMS College of Pharmacy, near RTO, keneedi road, Pune

Shridhar J Pandya

Shridhar J Pandya

E mail: shridhar_pandya@yahoo.co.in , : hari_dommati@yahoo.com

Contact no: +919924590576 , +919823841774

D Harinarayana

D Harinarayana

Devendra. K. Jain

Devendra. K. Jain

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