| Abstract [eng] |
Aim of the thesis: to investigate and evaluate the use of microneedles as the supply systems of medicinal substances in order to improve their supply and penetration through the skin in ex vivo conditions. Tasks of the thesis: to model the microneedles and evaluate the microdisturbances caused by them; to conduct penetration studies ex vivo and to evaluate the permeability of anesthetic medicinal substances (lidocaine and tetracaine) to the skin from different carriers; using the method of FT-IR spectroscopy, to evaluate potential interactions between lidocaine and tetracaine. Methodology of the thesis: ex vivo skin penetration studies have been performed using Bronaugh type flux diffusers. For research on human skin, a permit was received from Kaunas Regional Biomedical Research Ethics Committee (2014-07-14, No. BE-2-41). Results of the thesis: using microneedles of P200×A600, P300×A400 ir P300×A600 in size, higher levels of both lidocaine and tetracaine were found in the dermis compared to the epidermis, when ethanol blend of 7 percent lidocaine and 7 percent tetracaine wass used for the study. The amount of lidocaine in the skin layers using the 7 percent lidocaine solution was lower compared to the control, and the tetracaine content using the 7 percent tetracaine solution showed a significant increase (p<0.05). After evaluating the results, the area of the microneedles at the base had no effect on penetration. Comparing the permeation of lidocaine and tetracaine through the skin, it was found that a better penetration rate was obtained from the mixture of lidocaine and tetracaine ethanol. The study with microneedles coated with a drug substance film, showed that the penetration of substances into the skin did not improve. These results could be due to the lack of water in the skin, which could have prevented the effective solubility of the substances and their migration to the skin layers. Another reason – insufficient amount of the substance formed on the microneedles. This could have resulted in small amounts of lidocin and tetracaine penetration in the skin. Conclusions: the results of the study provided additional insights into the penetration rate of lidocaine and tetracaine using microneedles as penetration promotion systems. It has been found that using an eutectic 7 percent lidocaine and 7 percent tetracaine ethanol blend provides better penetration of anesthetic medicinal substances into the skin. The formation of a drug substance film from ethanol and aqueous solutions of lidocaine and tetracaine on the microneedles and determination of their amounts in the skin was found not to improve skin penetration. |
