Search

The aim of present study was to develop an oxybutynin (OXY) transdermal patch with good permeation behavior and mechanical property. Special attention was paid to the effect of chemical enhancer on the molecular mobility of pressure sensitive adhesive (PSA) at molecular level. PSAs and permeation enhancers were investigated through in vitro experiment using rat skin. The optimized formulation was evaluated through pharmacokinetic study using rat. In addition, the molecular mechanism of sorbitan monooleate (Span® 80) in the improvement of PSA molecular mobility was investigated using FT-IR, molecular dynamics simulation, DSC and rheological study. As a result, the optimized formulation using amide PSA demonstrated good adhesion property. And the AUC 0-t and C max of optimized patch were 6435.8 ± 747.8 h ∗ ng/mL and 127.8 ± 18.0 ng/mL, respectively, which had no significant difference with commercial product. Furthermore, the improvement of the PSA mobility by Span® 80 rather than the decrease of interaction between drug and PSA was the main factor that enhanced the release of OXY from patch. In conclusion, a drug-in-adhesive OXY patch was developed, and the effect of PSA molecular mobility increase on the enhancement of drug skin permeation was proposed at molecular level., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Certain mixtures of chemicals are known to synergistically enhance skin permeability to drugs. Here, we report on the transport enhancing properties of mixtures of an anionic surfactant, sodium lauroylsarcosinate (NLS) and a non-ionic surfactant, sorbitan monolaurate (S20) in 1:1 phosphate buffered saline (PBS):ethanol (EtOH) solvent. Effect of 44 different compositions of NLS:S20 on skin constituents was probed by Fourier transform-infrared (FT-IR) spectroscopy while behavior of surfactant molecules in the solvent system was probed by FT-IR and NMR spectroscopy. No aggregation of NLS or S20 alone was observed in 1:1 PBS:EtOH at all concentrations studied (0-2%, w/v). However, mixtures of NLS and S20 resulted in micelle-like aggregates at certain specific compositions. Interestingly, compositions with increased aggregation showed resemblance to those that exhibited highest skin permeabilization.