Purpose:  To investigate the effect of different solvents on the in vitro skin permeability of vitamin B₁₂.

Method: Vitamin B₁₂ (B₁₂) permeability experiments through rat skin pretreated with various solvents namely, propylene glycol, oleoyl macrogol-6-glycerides, propylene glycol monocaprylate and oleic acid, were performed in Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (J_ss), lag time (T_lag)_, permeability coefficient (Kp) and diffusion coefficient (D). The solvents’ permeability enhancement mechanisms were investigated  by comparing of changes in peak position and their intensities of assymmetric (Asy) and symmetric (Sym) C-H stretching, and C=O stretching absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (∆H) using differential scanning calorimetery (DSC).

Results: All the solvents significantly decreased diffusion coefficient (p < 0.05), with capryol showing the greatest enhancement ratio (ER_D) based on diffusion coefficient   followed by labrafil, oleic acid and propylene glycol. Flux enhancement ratio (ER_flux) for all the solvents was < ER_D. The solubility of B₁₂ in stratum corneum was the rate-limiting step in partitioning. All solvents with different lipophilic properties decreased drug solubility in the stratum corneum and hence lowered partitioning and flux. FTIR and DSC results showed lipid fluidization and extraction by labrafil and capryol, disruption of lipid structure and fluidization by oleic acid, and interaction with stratum corneum keratin by propylene glycol.

Conclusion: Water is a suitable topical vehicle for B₁₂ as it can increase partitioning and diffusion through rat skin.