Carbomers are synthetic high-molecular-weight polymers of acrylic acid that are used as versatile excipients in pharmaceutical formulations. Lubrizol is the pioneer and global leader in the carbomer field. 路博润的 ® Carbopol聚合物辅料 are well-established, pharmaceutical-grade excipients used in a broad range of drug formulations, including oral and topical dosage forms.

Lubrizol's Carbopol® polymer excipients are produced under cGMP conditions using dedicated manufacturing equipment and procedures. Each batch is tested and certified to meet the US Pharmacopoeia (USP-NF), the European Pharmacopoeia (EP), the Chinese Pharmacopoeia (ChP), and the Indian Pharmacopoeia (IP) monograph standards.

Are All Carbomer Polymers Safe?

Over the years, other manufacturers have introduced "me too" grades of carbomer polymers for pharmaceutical applications. While they often claim equivalency to Carbopol® polymer excipients, Lubrizol has identified quality and compliance issues with these alternate carbomers.

In multiple instances where customers who switched to alternate carbomers, many have experienced quality and consistency issues. and have discontinued using alternate carbomers in favor of Carbopol® polymer excipients.

Pharmacopoeia and Regulatory Compliance

Pharmacopeia compliance involves meeting the requirements specified in individual monographs, as well as adhering to all applicable GMP requirements. The International Pharmaceutical Excipients Council (IPEC) guide, Qualification of Excipients for Use in Pharmaceuticals, states:

It is not acceptable to purchase a "technical" or "industrial" or "food" grade material and simply test it using compendial monographs to confirm that it conforms to compendial specification limits. Without production in conformance to appropriate GMP requirements, the material remains unsuitable for use as an excipient
It is not appropriate for a supplier to offer a non-pharmaceutical grade material as an excipient

Regulatory Considerations for Class 1 Solvents in Pharmaceutical Excipients

Residual solvents are a key consideration for formulators using pharmaceutical excipients who need to ensure compliance with various compendial standards, including USP <467> and Eur. Ph 5.4. The International Council for Harmonization (ICH) develops globally harmonized guidelines to ensure the development of safe, effective, and high-quality medicines. To meet ICH guideline standards, pharmaceutical manufacturers need information on residual solvents in excipients or drug substances.

ICH Q3C (R9) is the primary guideline governing solvent used in API and drug manufacture. It applies to organic volatile solvents that may remain as residual impurities in APIs, excipients and finished drug products. The guideline categorizes solvents into three classes, based on their toxicity and potential health or environmental risks:

Class 1 solvents, such as 1,2-dichloroethane, are known or suspected carcinogens/environmental hazards that should not be used for manufacturing drug substances, excipients, or drug products (Table 1). US, European, and other country-specific pharmacopoeias subsequently limit their use in pharmaceutical applications. If Class 1 solvent use is unavoidable when manufacturing a drug product with a significant therapeutic advantage, levels should be restricted to very low allowable limits
Class 2 solvents, such as dicholoromethane and cyclohexane, have toxic effects and must be strictly controlled, based on their Permitted Daily Exposure (PDE)
Class 3 solvents, such as ethyl acetate, have low toxicity and are acceptable if total daily exposure does not exceed 50mg (≤5000ppm)

Table 1: Class 1 solvents in finished pharmaceutical products (solvents to be avoided)

溶剂	Concentration limit (ppm)	Concern
苯	2	Carcinogen
Carbon tetrachloride	4	Toxic and environmental hazard
1,2-dichloroethane	5	Toxic
1,1-dichloroethane	8	Toxic
1,1,1-trichloroethane	1500	Environmental hazard

Comparison of Lubrizol Carbopol® Polymer Excipients and Alternate Carbomer Polymers

Lubrizol fully declares the solvents involved in Carbopol® polymer excipient synthesis, whereas alternate carbomer manufacturers do not provide declarations regarding the use of Class 1 solvents (Table 2).

Table 2: Residual solvents for Carbopol® polymer excipients vs alternate carbomers

溶剂	Lubrizol Carbopol® polymer excipients*	Alternate carbomer 1	Alternate carbomer 2
Polymerization solvent	Ethyl acetate (Class 3) or a mixture of ethyl acetate and cyclohexane (Class 2)	1,2-dichloroethane (Class 1)	Methylene chloride (Class 2)
Residual solvent level	Consistent low amount of residual solvent	Very high levels of residual solvent; not specified or reported	Complies
Limit of ethyl acetate and cyclohexane	Complies	Not detected**	Complies
Limit of benzene	Complies	Not detected**	Complies

*Carbomer homopolymer type A - Carbopol® 71G NF, 971P NF and 981 NF polymer excipients; carbomer homopolymer type B - Carbopol® 974P NF and 5984 EP polymer excipients; carbomer homopolymer type C - Carbopol® 980 NF polymer excipients. Compendial method or cross-validated house method

**Certificate of analysis for alternate carbomer 1 has specifications for residual solvents: cyclohexane NMT 0.3% and ethyl acetate NMT 0.5%

并非所有卡波姆的配方都相同