Functional Category
Antimicrobial preservative; disinfectant
Applications in Pharmaceutical Formulation
Cresol is used at 0.15–0.3% concentration as an antimicrobial preservative in intramuscular, intradermal, and subcutaneous injectable pharmaceutical formulations. It is also used as a C Cresol 203 preservative in some topical formulations and as a disinfectant. Cresol is not suitable as a preservative for preparations that are to be freeze-dried.(1)
Description
Cresol consists of a mixture of cresol isomers, predominantly mcresol, and other phenols obtained from coal tar or petroleum. It is a colorless, yellowish to pale brownish-yellow, or pink-colored liquid, with a characteristic odor similar to phenol but more tarlike. An aqueous solution has a pungent taste.
Stability and Storage Condition
Cresol and aqueous cresol solutions darken in color with age and on exposure to air and light. Cresol should be stored in a well-closed container, protected from light, in a cool, dry place
Incompatibilities
Cresol has been reported to be incompatible with chlorpromazine.(4) Antimicrobial activity is reduced in the presence of nonionic surfactants
Safety
Reports of adverse reactions to cresol are generally associated with the use of either the bulk material or cresol-based disinfectants, which may contain up to 50% cresol, rather than for its use as a preservative. However, a recent case of cutaneous hypersensitivity reaction to the m-cresol component of an insulin formulation detected via intradermal and patch testing has been reported.(5) Cresol is similar to phenol although it is less caustic and toxic. However, cresol is sufficiently caustic to be unsuitable for skin and wound disinfection. In studies in rabbits, cresol was found to be metabolized and excreted primarily as the glucuronide.(6) A patient has survived ingestion of 12 g of cresol though with severe adverse effects.(7) LD50 (mouse, oral): 0.76 g/kg(8) LD50 (rabbit, skin): 2 g/kg LD50 (rat, oral): 1.45 g/kg See also Sections 17 and 18.