The Flux of Select NSAIDs through Silicone Membranes from Mineral Oil.

Paul S Mertz,Kenneth B Sloan

doi:10.3390/pharmaceutics6030354

Abstract

Here we report the experimental log maximum fluxes of n = 9 non-steroidal anti-inflammatory drugs (NSAID) through silicone membranes from the lipid mineral oil (experimental (Exp.) log JMPMO) and correlate those Exp. log JMPMO values with their experimental log maximum fluxes through human skin in vivo from mineral oil (Exp. log JMHMO). The correlation was only fair (r2 = 0.647) for n = 9 but improved dramatically if Nabumetone was removed from the correlation (n = 8, r2 = 0.858). Non-linear regression of the n = 8 Exp. log JMPMO values as the dependent variable against their log solubilities in mineral oil (log SMO) and in pH 7.4 or 1.0 buffers (log S7.4 or S1.0, respectively), and their molecular weights as independent variables in the Roberts–Sloan (RS) equation gave a new set of coefficients for the independent variables in RS. Those coefficients have been used to calculate log JMPMO values which have been correlated with the Exp. log JMPMO values to give r2 = 0.911 if log S7.4 and r2 = 0.896 if log S1.0 were used as aqueous phases. Thus, silicone membranes appear to be good surrogates for predicting flux through human skin if the vehicle is a lipid such as mineral oil.

Highlights

In the presently available literature, there is an increasing body of information examining whether the flux of pharmaceuticals through silicone membranes can serve as a surrogate for flux through human or animal skin [1,2]
Where D is the diffusion coefficient, L is the thickness of the membrane, CM1 is the concentration of the molecule in the first few layers of the membrane, CMn is the concentration in the last few layers of the membrane, SM1 is the solubility in the first few layers of the membrane, SVEH is the solubility in the vehicle (VEH), SAQ is the solubility in water (AQ), KM1:VEH is the partition coefficient for the molecule between the first few layers of the membrane M1 and the vehicle and KM1:AQ is the partition coefficient where the vehicle is water
The first analysis performed was how well the experimentally determined flux through silicone membrane compared with the human skin in vivo dataset published by Wenkers and Lippold [6]

Summary

Introduction

In the presently available literature, there is an increasing body of information examining whether the flux of pharmaceuticals through silicone membranes can serve as a surrogate for flux through human or animal skin [1,2]. The need for this alternative method of predicting transdermal drug delivery arises in part due to the European Union’s ban on topical drug or cosmetic formulations tested on animals [3].

Methods

Results

Conclusion