The effect of solvent on permeant diffusion through membranes studied using ATR‐FTIR and chemometric data analysis

• Published in: Journal of pharmaceutical sciences Vol. 93; no. 1; pp. 186 - 196
• Main Authors: Dias, M., Hadgraft, J., Raghavan, S.L., Tetteh, J.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.01.2004; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: ATR-FTIR; Biological and medical sciences; diffusion; Diffusion - drug effects; factor analysis; General pharmacology; Medical sciences; Membranes, Artificial; multivariate; Permeability - drug effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; skin penetration enhancers; Solubility - drug effects; solvent effects; Solvents - analysis; Solvents - pharmacokinetics; Spectroscopy, Fourier Transform Infrared - methods; skin penetration enhancers; multivariate; factor analysis; diffusion; solvent effects; ATR‐FTIR; Solvent effect; Membrane; Data analysis; Pharmaceutical technology; Diffusion
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10530

One method of improving the bioavailability of a topical formulation is to add an appropriate solvent that will act as a solubilizer for the permeant and, at the same time, modify the barrier properties of the stratum corneum. It has proved very difficult to determine the precise mechanisms of action involved; this is complicated by the concurrent diffusion of the solvent and the permeant into the skin. Under these circumstances the barrier function may well be changing as a function of time as the solvent disrupts it. We have observed this phenomenon in a model silicone membrane system that we have chosen to study initially to avoid the complexity of the heterogeneous nature of skin and its inherent biological variability. Diffusion experiments were conducted using an established ATR‐FTIR approach but the data interpreted using sophisticated chemometric approaches that allowed us to deconvolve the IR signals from the permeant, the solvent, and the membrane. Data are presented that show the concurrent diffusion of benzoic acid (permeant), octanol (solvent), and how the octanol modifies the characteristics of the silicone membrane. Initial data are then presented using human skin to show the power of the diffusion approach coupled to the data deconvolution technique. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:186–196, 2004