US EPA

4674227 

Journal Article 

Synergistic effect of 1,4-cyclohexanediol and 1,2-hexanediol on percutaneous absorption and penetration of metronidazole 

Li, N; Jia, W; Zhang, Y; Tan, F; Zhang, J 

2011 

Yes 

International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476 

415 

1-2 

169-174 

English 

21669264 

10.1016/j.ijpharm.2011.05.069 

WOS:000293304900022 

The objective of this study was to investigate the percutaneous absorption of metronidazole (MTZ) in the topical formulations containing a combination of 1,4-cyclohexanediol and 1,2-hexanediol. Six formulations were studied in an in vitro hairless mouse skin model using Franz Diffusion Cell. MTZ was applied at infinite doses (50mg and 100mg of the formulations, which correspond to 375 and 750 μg of MTZ, respectively). Based on the flux values and retardation ratio (RR), a synergistic retardation effect on percutaneous absorption of MTZ was observed for the formulations containing a combination of 1,4-cyclohexanediol and 1,2-hexanediol (RRs are 0.40 for 375 μg dose and 0.69 for 750 μg dose, respectively). Interestingly, retention of MTZ in epidermis and dermis layer showed no significant differences (p>0.05) between the formulations containing the retardant combination and control formulations. In other words, the retardant combination in the formulation decreases MTZ fluxes while maintaining similar level of retention in epidermis and dermis layer when compared to the control formulations. These observations provide insight in formulating superior topical formulations with minimized potential systematic toxicity while maintaining therapeutic efficiency. A mechanistic explanation of the observed synergistic effect is proposed. 

Index Medicus; 2011