Design and efficacy evaluation of innovative preparation methods for drug loaded transdermal applications

Transdermal drug delivery systems are one of the drug delivery systems, enabling the transport of the drug to the systemic circulation through the skin. Montelukast sodium (MS), was used as an active ingredient in our studies, which includes innovative approaches have been developed for the production techniques of patches and microneedles as transdermal drug delivery systems. Three-dimensional (3D) printer filaments were produced with hot melt extrusion (HME) method. The mechanical strengths of the filaments were investigated and used with the 3D printer for fabrication of patches. Characterization studies of MS was carried out. Quantitative determination of MS by high performance liquid chromatography has been developed and validated. As the stress tests, the stability of MS with heat and light exposure was investigated. In addition to the FT-IR, DSC, TGA and UV spectrum analyzes, solubility, lipid/water partition coefficient analyzes were also carried out. Following the characterization studies, MS loaded patches were produced with a 3D printer and mechanical tests and in vitro release studies were performed. Filaments made of poly(lactic acid) which are frequently used in 3D printers and the patches prepared by using these filaments were used for comparison. Microneedles made of pure MS were fabricated with molding method and maximum loading capacity was achieved. Imaging studies of microneedles were followed by mechanical analyzes. In vitro and ex vivo release studies were carried out. Stability of microneedles were examined in terms of MS amount and mechanical properties. In vitro transdermal permeation studies and ability of perforation of keratinocyte layer of microneedles were carried out with skin models. In vitro cytotoxicity and irritation studies were realized to investigate the biocompatibility of MS and microneedles. Morphology of the surface of the tissue was investigated with scanning electron microscope and histology studies were conducted with hematoxylin eosin staining methods. As the result of our studies, patches and microneedles have been developed for MS, which has only orally administered pharmaceutical forms. By transdermal administration of MS, the first pass effect would be avoided and the bioavailability would be increased additionally an alternative route of administration to the oral route may be constituted for the patients who cannot use oral route. It is envisaged that developed production methods, various transdermal drug delivery systems can be used with different active ingredients for improving the quality of patients.