Physico-chemical determinants of dermal drug delivery: effects of the number and substitution pattern of polar groups

• Published in: European journal of pharmaceutical sciences Vol. 16; no. 3; pp. 107 - 112
• Main Authors: du Plessis, Jeanetta, Pugh, W.John, Judefeind, Anja, Hadgraft, Jonathan
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.08.2002; Elsevier
• Subjects: Administration, Cutaneous; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Dipolar bonding; Epidermis - metabolism; Female; General pharmacology; Humans; Hydrogen bonding; Hydrogen Bonding - drug effects; Hydroxides - chemistry; Medical sciences; Molecular Structure; Permeability - drug effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phenols; Phenols - chemistry; Skin permeability; Solubility parameters; Phenols; Skin permeability; Dipolar bonding; Solubility parameters; Hydrogen bonding; Human; Transdermal system; Pharmaceutical technology; Solubility; Epidermis; Lipophily; Permeability; Dispersion; Polar bond; Dosage form; Skin; Diffusion; Physicochemical properties; Hydrogen bond
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(02)00085-4

The aim of this study was to investigate the effect of number and substitution pattern of –OH groups of a set of phenols on the in vitro permeation of heat-separated human epidermis. The diffusion was calculated from Log( D/ x)=log k p−0.59 log K oct+0.024 ( D, diffusion coefficient; x, pathlength; k p, permeability coefficient (cm/h); and K oct, octanol–water partition coefficient). The main factors reducing D were the dipolar and hydrogen bonding capabilities of the permeants quantified as their Hansen partial solubility parameters δ p and δ h. These parameters are significantly reduced by the degree of symmetry of the molecule, so that phloroglucinol (1,3,5-benzenetriol), with three –OH groups, diffuses more rapidly that phenol. When symmetry is absent, as in 1,2,4-benzenetriol, the number of –OH groups results in very slow diffusion. D/ x (cm/h) was related to the combined solubility parameter δ a defined as √( δ p 2+ δ h 2) by: ( D/ x)=0.0024−0.000065 δ a ( n=7, R 2=0.70, P=0.012).