Journal of Controlled Release 2002-07-18

Quantitative evaluation of adhesive properties and drug-adhesive interactions for transdermal drug delivery formulations using linear solvation energy relationships.

Jianwei Li, Jeremy J Masso, Stanley Rendon

文献索引：J. Control. Release 82(1) , 1-16, (2002)

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摘要

This paper describes the results of the application of linear solvation energy relationships (LSERs) to quantitatively characterize the properties of adhesives and to evaluate the degree of drug-adhesive interaction in transdermal drug delivery formulations. Probe solutions were prepared in acetonitrile (ACN) for a set of probe compounds with different physicochemical properties, and were used to swell the adhesives for subsequent probe molecule-adhesive interactions. The degree of the interactions was measured by the 'sorbed' amount of probe molecules. Based on LSERs, the 'sorbed' amounts were linearly correlated with their properties. The corresponding coefficients reflect the differential interactions of these molecules with the adhesive and ACN, and are quantitative indications of the adhesive properties. Two different transdermal acrylate adhesives (isooctyl acrylate/acrylamide/vinyl acetate in the weight ratios of 75/5/20 and isooctyl acrylate/2-hydroxyethyl acrylate/vinyl acetate in the weight ratios of 58/20/18) were selected for the evaluation of the methodology. It is concluded that the first adhesive is more basic and hydrophobic, which is consistent with the use of acrylamide monomer and significant amount of isooctyl acrylate. The second adhesive is more acidic and polarizable due to a relatively high amount of the 2-hydroxyethyl acrylate. Additionally, the 'sorbed' amount can be regarded as an interaction parameter or index between a drug molecule and the adhesive. Finally, this parameter is expected to correlate with the thermodynamic properties of transdermal formulations such as drug solubility, diffusion coefficient, release rate, and maybe skin permeation rate.Copyright 2002 Elsevier Science B.V.