Carbomer 980P

Category

Carrier Excipients

Molecular Weight

/

Grade

Pharmceutical Excipients

Description

Carbomers are white-colored, ‘fluffy’, acidic, hygroscopic powders with a characteristic slight odor. A granular carbomer is also available (Carbopol 71G).

UNII

NA

Chemical Name

Carbomer 980

CAS Number

139637-85-7

Synonyms

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Administration route

Oral; ophthalmic, rectal, topical, transdermal ;
vaginal

Dosage Form

Oral suspensions, tablets; ophthalmic, rectal, topical, transdermal preparations;
vaginal suppositories

Stability and Storage Conditions

Carbomers are stable, hygroscopic materials that may be heated at temperatures below 1048C for up to 2 hours without affecting their thickening efficiency. However, exposure to excessive temperatures can result in discoloration and reduced stability. Complete decomposition occurs with heating for 30 minutes at 260℃. Dry powder forms of carbomer do not support the growth of molds and fungi. In contrast, microorganisms grow well in unpreserved aqueous dispersions, and therefore an antimicrobial preservative such as 0.1% w/v chlorocresol, 0.18% w/v methylparaben-0.02% w/v propylparaben, or 0.1% w/v thimerosal should be added. The addition of certain antimicrobials, such as benzalkonium chloride or sodium benzoate, in high concentrations (0.1% w/v) can cause cloudiness and a reduction in viscosity of carbomer dispersions. Aqueous gels may be sterilized by autoclaving with minimal changes in viscosity or pH, provided care is taken to exclude oxygen from the system, or by gamma irradiation, although this technique may increase the viscosity of the formulation. At room temperature, carbomer dispersions maintain their viscosity during storage for prolonged periods. Similarly, dispersion viscosity is maintained, or only slightly reduced, at elevated storage temperatures if an antioxidant is included in the formulation or if the dispersion is stored protected from light. Exposure to light causes oxidation that is reflected in a decrease in dispersion viscosity. Stability to light may be improved by the addition of 0.05-0.1% w/v of a water-soluble UV absorber such as benzophenone-2 or benzophenone-4 in combination with 0.05-0.1% w/v edetic acid. Carbomer powder should be stored in an airtight, corrosionresistant container and protected from moisture. The use of glass, plastic, or resin-lined containers is recommended for the storage of formulations containing carbomer.

Source and Preparation

Carbomers are synthetic, high-molecular-weight, crosslinked polymers of acrylic acid. These acrylic acid polymers are crosslinked with allyl sucrose or allyl pentaerythritol. The polymerization solvent used previously was benzene; however, some of the newer commercially available grades of carbomer are manufactured using either ethyl acetate or a cyclohexane-ethyl acetate cosolvent mixture. The Carbopol ETD and Carbopol Ultrez polymers are
produced in the cosolvent mixture with a proprietary polymerization aid.

Applications

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.

Safety

Carbomers are used extensively in nonparenteral products, particularly topical liquid and semisolid preparations. Grades polymerized in ethyl acetate may also be used in oral formulations. There is no evidence of systemic absorption of carbomer polymers following oral administration.Acute oral toxicity studies in animals indicate that carbomer 934P has a low oral toxicity, with doses up to 8 g/kg being administered to dogs without fatalities occurring. Carbomers are generally regarded as essentially nontoxic and nonirritant materials; there is no evidence in humans of hypersensitivity reactions to carbomers used topically.
LD50 (guinea pig, oral): 2.5 g/kg for carbomer 934
LD50 (guinea pig, oral): 2.5 g/kg for carbomer 934P
LD50 (guinea pig, oral): 2.5 g/kg for carbomer 940
LD50 (mouse, IP): 0.04 g/kg for carbomer 934P
LD50 (mouse, IP): 0.04 g/kg for carbomer 940
LD50 (mouse, IV): 0.07 g/kg for carbomer 934P
LD50 (mouse, IV): 0.07 g/kg for carbomer 940
LD50 (mouse, oral): 4.6 g/kg for carbomer 934P
LD50 (mouse, oral): 4.6 g/kg for carbomer 934
LD50 (mouse, oral): 4.6 g/kg for carbomer 940
LD50 (rat, oral): 10.25 g/kg for carbomer 910
LD50 (rat, oral): 2.5 g/kg for carbomer 934P
LD50 (rat, oral): 4.1 g/kg for carbomer 934
LD50 (rat, oral): 2.5 g/kg for carbomer 940
LD50 (rat, oral): > 1g/kg for carbomer 941
No observed adverse effect level (NOAEL) (rat, dog, oral): 1.5 g/kg for carbomer homopolymer type B.

Incompatibilities

Carbomers are discolored by resorcinol and are incompatible with phenol, cationic polymers, strong acids, and high levels of electrolytes. Certain antimicrobial adjuvants should also be avoided or used at low levels. Trace levels of iron and other transition metals can catalytically degrade carbomer dispersions. Certain amino-functional actives form complexes with carbomer; often this can be prevented by adjusting the pH of the dispersion and/or the solubility parameter by using appropriate alcohols and polyols. Carbomers also form pH-dependent complexes with certain polymeric excipients. Adjustment of pH and/or solubility parameter can also work in this situation.