The effect of lipid and aqueous solubilities on flux of nicotinic acid esters from water through silicone membrane

Abstract

Objective: The maximum fluxes (J_M) of nicotinic acid esters (NAE) across silicone membranes from water (J_MPAQ) have been measured to determine how well they correlate with J_M of NAE across human skin from water in vitro (J_MHAQ) and in vivo (J_MHAQ1) and with J_M of NAE across hairless mouse skin from water (J_MMAQ).

Materials and methods: The NAE were all commercially available. Solubilities in water (S_AQ), isopropyl myristate (S_IPM) and octanol (S_OCT) were obtained from literature sources. J_MPAQ were measured at saturation for all the esters except the methyl ester. In that case, flux was measured at a concentration (C) less than saturation (J_PAQ) and converted to J_MPAQ = (J_PAQ)(S_AQ/C_AQ).

Results and discussion: J_MPAQ values predicted from the previously reported coefficients to the parameters in the Roberts-Sloan (RS) equation (PRE J_MPAQ) were substantially lower than the experimental J_MPAQ values (EXP J_MPAQ) values obtained here. The EXP J_MPAQ were incorporated into the previous J_MPAQ database and new coefficients were obtained: x = −1.837; y = 0.742; z = 0.00435; r² = 0.86. Correlation of J_MPAQ values with J_MHAQ, J_MHAQ1, and J_MMAQ values show the same trend as the J_MPAQ values.

Conclusions: The inclusion of the NAE n = 6 data into the previous n = 32 database for the permeation of the prodrugs through a silicone membrane from water (J_MPAQ) greatly improved the fit of the n = 38 database to the RS equation: r² = 0.86 vs r² = 0.77. The correlation between log J_MHAQ and log J_MPAQ gave r² = 0.98. This suggests that J_MPAQ values are good predictors of J_MHAQ values.

Keywords::

• Maximum flux
• molecular weight
• flux through human skin in vivo and in vitro
• Franz diffusion cell
• Roberts-Sloan equation
• Kasting-Smith-Cooper equation
• Potts-Guy equation