PubMed · 12106759
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L M Keder. 2002. New developments in contraception.. https://doi.org/10.1016/s1083-3188(02)00140-7
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The development of a transdermal delivery system for isosorbide dinitrate (ISDN) using electron beam irradiation was studied. The solid state stability of the drug to irradiation was assessed. The drug was dissolved in 2-ethylhexylacrylate (EHA)-acrylic acid (AA) system and this solution was directly irradiated on a backing membrane (Scotchpak1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratios (EWSR), differential scanning calorimetry (DSC), weight uniformity, thickness uniformity, drug content and content uniformity, peel strength, in vitro release, skin permeation kinetics and skin irritation potential. The developed system possessed excellent adhesive properties. Increase in the irradiation doses did not have a significant effect on the peel strength values. The systems exhibited promising skin permeation kinetics and no skin irritating potential, both of which are important properties for transdermal drug delivery. The ISDN-EHA-AA system developed at an irradiation dose of 50 kGy showed a higher skin permeation profile as compared to an internationally marketed transdermal matrix system of ISDN.
Deformable liposomes were prepared to investigate the effectiveness of dermal administration of methotrexate (MTX). The phospholipids used to prepare the liposomes were soybean lecithin (PC) or hydrogenated lecithin (HPC) and dipotassium glycyrrhizinate (KG) as surfactant. The lipid/KG ratio (w/w) was 2:1 and 4:1. Liposomes size, entrapment efficiency and MTX release through dialysis membrane were determined and the interaction between MTX and liposomes was investigated using differential scanning calorimetry. The MTX amount permeated through pig skin were three- to four-fold higher using liposomes containing KG compared to those from water solution or normal liposomes. No significant differences were observed between PC-KG liposomes and HPC-KG liposomes. At the end of the skin permeation assay using deformable liposomes, up to 50% of the administered dose was found in the skin. This capability depends on the self-regulating carrier deformability. These results suggest that liposomes containing KG may be of value for the topical administration of MTX in the treatment of psoriasis.
The influence of iontophoresis and other physical enhancement methods such as electroporation and erbium:yttrium-aluminum-garnet (YAG) laser on the skin permeation of 5-fluorouracil (5-FU) was examined. Iontophoresis increased the in vitro transdermal transport of both the anionic and non-ionic forms of 5-FU. A combination of electroporation pretreatment and subsequent iontophoresis resulted in a higher permeation of 5-FU than either technique alone. It appeared that electroporation treatment exerted a disruptive influence on the stratum corneum (SC). The SC layers in the skin were partly ablated by the laser, resulting in a great enhancement effect on the skin permeation of 5-FU. Application of iontophoresis further increased the drug permeation across laser-pretreated skin. The laser was consistently the most potent technique to enhance 5-FU delivery among the physical enhancement methods examined in this study.