Name: Polycarbophil
CAS No: Polycarbophil [9003-97-8]
USP: Polycarbophil
Noveon AA-1.
Polycarbophil [9003-97-8]
Polycarbophil is a high molecular weight acrylic acid polymer crosslinked with divinyl glycol. The molecular weight of this polymer is theoretically estimated to range from 700 000 to 3–4 billion. However, there are no methods currently available to measure the actual molecular weight of a crosslinked (i.e. threedimensional) polymer of this type.
Conventionally, polycarbophil is used as a thickening agent at very low concentrations (less than 1%) to produce a wide range of viscosities and flow properties in topical lotions, creams, and gels, in oral suspensions, and in transdermal gel reservoirs. It is also used as an emulsifying agent in topical oil-in-water systems. Polycarbophil is an excellent bioadhesive in buccal, ophthalmic, intestinal, nasal, vaginal, and rectal applications. Buccal tablets prepared using polycarbophil have shown high bioadhesive force and prolonged residence time, and proved to be nonirritative in in vivo trials with human buccal mucosa.(1) Polycarbophil has been used in combination with hydroxypropyl methylcellulose to develop a bilayered buccal bioadhesive film formulation of nicotine hydrogen tartrate for smoking cessation therapy.(2) It is also useful in designing controlled-release formulations(3) and for drugs that undergo first-pass metabolism.(4) Polycarbophil buccoadhesive disks have also been developed in formulations increasing the bioavailability(5) and transmucosal absorption of poorly watersoluble drugs.(6) Sublingual tablets of buprenorphine formulated using polycarbophil have shown superior mucoadhesive strength when compared to those using carbomer.(7) Polycarbophil gels have been used for delivering bioactive substances for local application to gingival,(8) oropharyngeal(9) and periodontal(10,11) areas, and also for ocular drug delivery.(12) The nasal retention of plasmid DNA is highly prolonged with the use of polycarbophil as the gelling agent.(13) Polycarbophil has also been used to design an insulin liquid suppository for rectal application.(14,15) A vaginal gel of econazole has shown improved therapeutic benefit on topical application in vaginal candidiasis.(16) An intravaginal administration of polycarbophil gel alone and with carbomer is associated with improved signs of bacterial vaginosis.( 17,18) Polycarbophil with carboxymethylcellulose sodium are the polymers of choice for the formulation of an acid-buffering bioadhesive vaginal tablet of clotrimazole and metronidazole.(19) Mucoadhesive vaginal vaccine delivery systems using polycarbophil have proved to be effective in the induction of mucosal and systemic immune responses.(20) Polycarbophil gels have been used to deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) effectively to genital preneoplastic lesions.(21) Polycarbophil microspheres have been formulated for drug delivery to oral(22,23) and nasal(24) cavities. Floating-bioadhesive microspheres coated with polycarbophil have been found to be a useful gastroretentive drug delivery system for the treatment of Helicobacter pylori.(25) Conjugation with L-cysteine (thiolated polycarbophil) greatly enhances the mucoadhesive properties of polycarbophil(26) and can be used as a platform for oral(27) and nasal(28) polypeptide delivery (e.g. heparin,(29–31) human growth hormone,(32) insulin,( 33,34) antigens for oral protein vaccination(35)) and for ocular(36) and transdermal drug delivery systems.(37) These compounds have shown higher stability and more controlled drug release. They have also been reported to act as a permeation enhancer by triggering the reversible opening of the tight junctions between the cells, thereby allowing the paracellular transport of peptides, in addition to locally deactivating the most important enzymes of the gastrointestinal tract.(38,39) Due to its likelihood for inhibiting Pglycoprotein, thiolated polycarbophil has demonstrated improved bioavailability of an oral paclitaxel formulation.(40)
Polycarbophil occurs as fluffy, white to off-white, mildly acidic polymer powder with slightly acetic odor.
See Table I.
Acidity/alkalinity pH = 2.0–4.0 (1.0% w/v aqueous dispersion); pH = 2.7–3.5 (0.5% w/v aqueous dispersion). Ash content 0.009 ppm Density (bulk) 0.19–0.24 g/cm3 Dissociation constant pKa = 6.0 0.5 Equilibrium moisture content 8–10% (at 50% relative humidity) Glass transition temperature 100–1058C Moisture content 1.5% maximum for Noveon AA-1 Residual solvents Benzene 0.50 ppm for Noveon AA-1; Ethyl acetate 0.45% for Noveon AA-1. Solubility Polycarbophil polymers do not dissolve in water but can swell in water to around 1000 times their original volume (and ten times their original diameter) to form gels when exposed to a pH environment above 4–6. Since the pKa of these polymers is 6.0 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. Particle size distribution Polycarbophils are produced from primary polymer particles of an average diameter of about 0.2 mm. These polymers are then flocculated, resulting in powders averaging 2–7 mm in diameter. Once formed, the flocculated agglomerates cannot be broken down into their primary particles. Specific gravity 1.41
Polycarbophil polymers are stable, hygroscopic materials. They do not undergo hydrolysis or oxidation under normal conditions. Heat aging at temperatures below 1048C for up to 2 hours does not affect the efficiency of the dry polymer. However, prolonged exposure to excessive temperatures can result in discoloration, reduced stability, and in some cases plasticization of the polymer. Complete decomposition occurs with heating for 30 minutes at 2608C. Polycarbophil polymers do not support bacteria, mold, or fungal growth in dry powder form. Microbial growth may occur in mucilages of the polymer solution. Although the gel properties are not affected by such growth, this phenomenon is usually unacceptable. The addition of appropriate preservatives prevents mold and bacterial growth in these mucilages. Mucilages and emulsions containing these polymers are stable under freeze–thaw conditions but exposure to high temperatures results in a drop in viscosity. Polycarbophil polymers are very hygroscopic and should be packed in airtight, corrosion-resistant containers. They should be stored in a cool, dry place, and the container should be kept closed when not in use. Moisture pickup does not affect the efficiency of the resins, but resin containing high levels of moisture is more difficult to disperse and weigh accurately. Glass, plastic, or resinlined containers are recommended for products containing polycarbophil. Packaging in aluminum tubes usually requires formulations to have a pH less than 6.5, and packaging in other metallic tubes or containers necessitates a pH greater than 7.7 to prolong polycarbophil stability.
Heat may be generated if polycarbophil comes into contact with strong basic materials such as ammonia, sodium hydroxide, potassium hydroxide, or strongly basic amines. Polycarbophil polymers are not compatible with cationic polymers, strong acids, and high levels of electrolytes, as electrolytes tend to reduce the viscosity of polycarbophil-based gels.
Polycarbophils are synthetic, high-molecular-weight, crosslinked polymers of acrylic acid. These poly(acrylic acid) polymers are crosslinked with divinyl glycol. They are synthesized via precipitation polymerization in ethyl acetate and then dried.
Polycarbophil polymers have a long history of safe and effective use in topical gels, creams, lotions, and ointments. They have been shown to have extremely low irritancy properties and are nonsensitizing with repeated usage. The use of these polymers is supported by extensive toxicological studies.(41) LD50 (guinea pig, oral): 2.0 g/kg LD50 (mouse, IP): 0.039 g/kg LD50 (mouse, IV): 0.070 g/kg LD50 (mouse, oral): 4.6 g/kg LD50 (rat, oral): >2.5 g/kg LD50 (rabbit, skin): >3.0 g/kg Chronic oral toxicity No significant effects in rats or dogs were observed after being fed with resin as 5% of the diet for 61=2 months.
Observe normal precautions appropriate to the circumstances and quantity of material handled. Excessive dust generation should be minimized to avoid the risk of explosion (lowest explosive concentration is 130 g/m3). Polycarbophil dust is an irritant to eyes, mucous membranes, and the respiratory tract. Powder/dust eye irritation is a physical, not a chemical effect. Solid particles on the eye (powder/dust) may cause pain and be accompanied by irritation. A 1% physiological saline should be used for irrigation purposes. Dust inhalation may cause coughing, mucus production, and shortness of breath. Contact dermatitis may occur in individuals under extreme conditions of prolonged and repeated contact, high exposure, high temperature, and occlusion (being held onto the skin) by clothing. Gloves, eye protection, and a dust respirator are recommended during handling. Polycarbophil should be used in well-ventilated conditions.
GRAS listed. Included in the FDA Inactive Ingredients Database (buccal (tablet) and ophthalmic (solution) preparations; topical patches; vaginal gel). Included in nonparenteral medicines licensed in the UK.
Calcium polycarbophil; carbomer. Calcium polycarbophil Empirical formula Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. Molecular weight The molecular weight of these polymers is theoretically estimated to range from 700 000 to 3–4 billion. There are, however, no methods currently available to measure the actual molecular weight of a crosslinked (i.e. threedimensional) polymer of this type. CAS number [9003-97-8] Synonyms Noveon CA-1; Noveon CA-2. Appearance White powder with slightly acetic odor. Acidity/alkalinity pH = 6.0–8.0 (1% w/v aqueous dispersion) Density (bulk) 0.86 g/cm3 (Noveon CA-1); 0.55 g/cm3 (Noveon CA-2). Moisture content <10% Particle size distribution 75 mm (Noveon CA-1); 25 mm (Noveon CA-2). Pharmacopeial specifications see Table II. Safety LD50: (rat, oral): >2.5 g/kg LD50: (rabbit, skin): >3.0 g/kg Chronic oral toxicity No significant effects in rats or dogs were observed after being fed with resin as 5% of the diet for 6–12 months. Skin No evidence of irritation or sensitization during human patch testing. Regulatory status GRAS listed. Included in the FDA Inactive Ingredients Database (oral, troche). Comments Noveon CA-1 is a coarsely ground grade of calcium polycarbophil and is ideally suited for formulating swallowable bulk laxative tablets, while Noveon CA-2 is a finely ground grade and is designed for formulating chewable or swallowable bulk laxative tablets. Both grades swell in the intestinal tract, taking advantage of the natural water absorbency of polycarbophil. The swollen polycarbophil gel then acts as a bulk laxative as it moves through the gastrointestinal tract. Calcium polycarbophil is useful in improving colonic transit, bowel movements, stool form and abdominal pain in patients with irritable bowel syndrome.(42,43)
A novel interpolyelectrolyte complex of chitosan–polycarbophil has demonstrated a high potential as an excipient for the production of monolithic swellable matrix systems with controlled drug release properties.(44–46)