title: Stability of benzoyl peroxide in aromatic ester-containing topical formulations.
abstract: The chemical stability of benzoyl peroxide (BPO) was studied in solutions and gels. The solutions (1% w/v) were prepared in single solvents (alcohol USP, isopropyl alcohol USP, ethyl benzoate, C12-15 alkyl benzoate, dimethyl isosorbide, propylene carbonate, and acetone) and in binary and tertiary combinations of these solvents, with and without the addition of antioxidant(s) (BHT, BHA, eugenol, tert-butyl hydroquinone, Tenox-2, vitamin E, and vitamin C). The solutions were stored at 37 degrees C for 5 weeks, and each week were analyzed for remaining BPO. Using first-order kinetics, the stability of BPO in solution was found to decrease in the order: ternary>binary>single solvent systems. Regardless of the number of solvents present, the highest stability of BPO (t1/2>7.5 weeks) was attained in the presence of ethyl benzoate and C12-15 alkyl benzoate. The stability of BPO in solution did not change significantly with the addition of most antioxidants. The solutions in which BPO remained most stable were one in alcohol USP-ethyl benzoate-C12-15 alkyl benzoate (60:20:20; t1/2=18.15 weeks) and another in alcohol USP-C12-15 alkyl benzoate-isopropanol plus 0.1% BHT (65:20:15; t1/2=12.44 weeks). In turn, these two solutions were converted to homogeneous gels by the addition of Cab-O-Sil. The chemical stability of BPO in these gels was evaluated at 37 degrees, 45 degrees, 50 degrees, and 55 degrees C for 5 weeks. Parallel experiments were conducted with two commercial BPO products, a 2.5% tinted gel and 5% vanishing lotion. BPO was less stable in commercial products (t1/2<or=13 weeks) than in the extemporaneously prepared gels (mean t1/2 approximately 23 weeks). The present results suggest that aromatic esters can enhance the chemical stability of BPO in solutions and gel formulations to a significant extent.
authors.affiliation: Ortho-McNeil Pharmaceutical, a Johnson & Johnson Company, Raritan, NJ 08869, USA. bmajekod@psgus.jnj.com
authors.forename: Bola D
authors.initials: BD
authors.lastname: Majekodunmi
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Lau-Cam
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nash
mesh_terms: D019840:2-Propanol / Q000737:chemistry; D000096:Acetone / Q000737:chemistry; D000279:Administration, Cutaneous; D000975:Antioxidants / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry*; D001585:Benzoyl Peroxide / Q000737:chemistry*; D003879:Dermatologic Agents / Q000737:chemistry*; D004355:Drug Stability; D004952:Esters; D000431:Ethanol / Q000737:chemistry; D005782:Gels; D007547:Isosorbide / Q000031:analogs & derivatives / Q000737:chemistry; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013696:Temperature
chemical_list: D000975:Antioxidants; D001565:Benzoates; D003879:Dermatologic Agents; D004952:Esters; D005782:Gels; D012996:Solutions; D012997:Solvents; D000096:Acetone; D000431:Ethanol; C045990:propylene carbonate; D019840:2-Propanol; C040079:2,5-dimethylisosorbide; D011407:Propane; D001585:Benzoyl Peroxide; D007547:Isosorbide