Adsorption and release of nicotine from imprinted particles synthesised by precipitation polymerisation: Optimising transdermal formulations

Abstract

Molecularly imprinted polymers (MIPs) are promising materials that can be used as advanced pharmaceutical excipients in the development of formulations for sustained release of drugs. In previous studies, we developed formulations for the transdermal administration of nicotine based on MIPs synthesised by bulk polymerisation that were able to control skin permeation rate of the drug for 24 h following a Higuchi kinetic. In this work, we optimise the synthesis protocol using the precipitation polymerisation technique. MIPs, including the hydrophilic monomer 2-hydroxyethyl methacrylate (HEMA), were selected for their improved adsorption capacity and selectivity in comparison with non-imprinted polymers (NIPs). Adsorption data were better fitted to Langmuir-Freundlich model, indicating heterogeneity of the binding sites. MIPs showed swelling 3–5 times larger than NIPs in aqueous media, while swelling studies in mineral oil (non-polar vehicle) did not indicate differences between these materials. Formulations prepared using mineral oil as vehicle indicated that MIP-based formulations showed a faster release than those based on NIPs, which was related to their increased swelling with the release medium. Skin permeation studies using ear porcine skin indicated that MIP-based formulations with high nicotine loading were able to control the skin permeation flux following zero order kinetic for prolonged times (48 h). The permeation rate from these MIP formulations was lower than from NIP formulations. Thus, these results were associated with limited swelling of MIPs during in vitro skin permeation assays, and the selective desorption of nicotine from MIP particles.