Carbomer 940

Category

Suspending Agents; Thickener

Molecular Formula

(C3H4O2)n

Grade

Pharmceutical Excipients

UNII

4Q93RCW27E

Chemical Name

Cross-linked polyacrylic resin

CAS Number

9003-01-4

Synonyms

Acritamer; acrylic acid polymer; Carbopol; carboxy polymethylene, polyacrylic acid; carboxyvinyl polymer; Pemulen; Ultrez

Administration route

Topical; Ophthalmic; Transdermal

Dosage Form

Oral suspensions and tablets, ophthalmic preparations, rectal preparations and topical preparations

Stability and Storage Conditions

Carbomer is a stable and hygroscopic substance that does not affect its thickening when heated at 104℃ for 2 hours. However, exposure to excessive temperatures can reduce discoloration and stability. It is completely decomposed by heating at 260℃ for 30 minutes. Dry powdery carbomer does not grow mildew. In contrast, microbes grow well in preservative-free aqueous dispersions. Therefore, preservatives such as 0.1%(W/V) of chlorocresol, 0.18% (W/V) of hydroxyphenylene methyl, 0.02%(W/V) of hydroxyphenylene propyl, or 0.1%(W/V) of thiomersal should be added. The addition of certain bacteriostatic agents, such as benzalammonium chloride or sodium benzoate, at high concentrations (0.1%W/V) caused turbidity and decreased viscosity of carbomer dispersions. Hydrogels can be autoclaved. If the mixed oxygen is removed, there is only a small change in pH and viscosity. It can also be sterilized with gamma rays, but this technique can increase the viscosity of the preparation and extend the shelf life of carbomum at room temperature with the viscosity unchanged. If antioxidants are added to the preparation, or the dispersion is kept away from light, the viscosity of the dispersion remains the same, or there is a slight decrease, under the condition of increasing temperature. Light can cause oxidation, which is reflected in the reduction of viscosity of the dispersion. These changes can be improved by adding 0.05%~0.1% (W/V) of water-soluble UV absorbent such as benzophenone -2 or benzophenone -4 with 0.05%~0.1% (W/V) of EDTA. Triethanolamine as a neutralizer can also improve the stability of carbomer against UV. Carbomer powder should be stored in a cool, dry environment in an airtight anticorrosive container. Pharmaceutical preparations containing carbomer should be contained in glass, plastic, or resin-lined containers. The pH of the preparation should be less than 6.5 when packaged in aluminum tubes and more than 7.8 when packaged in other metal tubes or containers to improve carbomer stability.

Source and Preparation

Carbomer is a synthetic high molecular weight acrylic crosslinked polymer. It is prepared by crosslinking a poly (acrylic acid) polymer with propylene sucrose or allyl pentaerythritol. The most common solvent for polymerization is benzene. Newer Carbomer models are prepared using a mixture of ethyl acetate or cyclohexan-ethyl acetate solvents.

Applications

Carbomer is mainly used in liquid or semi-solid drug dosage forms as a suspension aid or viscosifier. Dosage forms include creams, gels, eye ointments, rectal and topical preparations. Even with only low residue benzene carbomer models such as Carbomer 934P. However, solvents other than "Class I OVI solvents" specified by ICH with low residues may be used in Europe. Containing only low-residue ethyl acetate carbomer, such as carbomer 971P or 974P, can be used in oral preparations, suspensions, tablets, or sustained-release tablets. Carbomer is used in tablets as a dry or wet binder and as a release rate control excipient. In wet granulation processes, water or ethanol-water mixtures may be used as wetting agents. Anhydrous organic solvents with polymer adhesives can also be used. The viscosity of the wet material decreases with the addition of some cationic substances into the granulating liquid. When water is available, adding talcum powder to the prescription can also reduce viscosity. Carbomol resin has been studied for the preparation of slow-release skeleton pellets, as an enzyme inhibitor of intestinal protease in preparations containing peptides, for cervical patches, and for intranasal administration microspheres. And locate the magnetic granules that drugs are delivered to the esophagus. Carbomer is also used as an emulsifier in O/W type emulsions for topical use. For this purpose, carbomer is partly neutralized with sodium hydroxide and partly with long-chain fatty amine and stearamine. Carbomer 952.as a viscosifier is also used in the preparation of multiemulsion microspheres. Carbomer is also commonly used in cosmetics.

Safety

Carbomer is widely used in non-injectable preparations, especially topical liquid and semi-solid preparations. There are certain levels that can be applied in oral preparations. Carbomer is generally considered to be basically non-toxic, non-irritating excipients. There is no evidence of anaphylaxis with topical carbomer, and human oral doses of carbomer of 1~3g can be used as a strong diarrhea agent. Carbomer 940 LD50 (Guinea pig, oral) : 2.5g/kg Carbomer 940 LD50 (mouse, IP) : 0.04g/kg Carbomer 940 LD50 (mouse, IV) : 0.07g/kg Carbomer 940 LD50 (mice, orally) : 4.6g/kg Carbomer 940 LD50 (rats, orally) : 2.5g/kg

Incompatibilities

Carbomol discoloration and incompatibility with phenol, cationic polymers, strong acids and high concentrations of electrolytes. Certain bacteriostatic agents should also be avoided or used in low concentrations. Trace amounts of iron or other transition metals can catalyze the degradation of carbomer solution. Carbomer produces large amounts of heat when in contact with a strong alkali such as ammonia, potassium hydroxide, sodium hydroxide, or a strong alkaline organic amine. Some drugs containing amino functional groups can form water-soluble complexes with carbomer. Usually this situation can be prevented by adjusting the solubility of the liquid with appropriate alcohol or polyol (solubility parameter). Carbomer and some polymer excipients can also form ph-dependent complexes, and the adjustment of solubility parameters can also be effective under such conditions.