OBJECTIVES The aim of this thesis is to describe, analyze and critically discuss essential factors affecting the efficacy of the dermal preparation. MATERIAL AND METHODS Search online databases was conducted electronically with a networked computer that has online access to databases PubMed, Elsevier and Science Direct. The literature was searched depending on the subject of the investigation, authors and the journals, from general to specialized articles. During investigation, the relevant articles were chosen and studied. The most important results, discussions and conclusions are shown in this thesis. Researching the database of scientific literature provides an overview of the latest findings on factors affecting the efficacy of the dermal preparation and the complex interaction of the active substance, the base and the skin. RESULTS Most classic drugs do not show satisfactory permeation through the skin, resulting in the development of innovative systems for delivering the active substance to the desired site of action. For example, microemulsions, solid lipid nanoparticles and nanostructured lipid carriers are developed, enabling larger doses of active substance and greater drug stability. The ability of such carriers to improve the permeation of the active substance through the skin and to achieve "targeting" of a broad spectrum of active substances depends on the composition of the base as well as on the physico-chemical properties of the active substance. The influence of the base on the absorption of the active substance is very complex because it depends on the physico-chemical interactions between the base and the active substance and on the interactions of the base with the skin surface. Of course, prior to all these interactions, a significant factor in the delivery of active substance to the skin is the physico-chemical properties of the active substance itself, namely: molecule size, polarity and lipophilicity. CONCLUSION Functional corneal barrier is the basis for skin health, which means that the balance of functional lipids, water and natural moisture factors should be maintained. To achieve this, the dermal formulation should contain harmonized amounts of water, emollients and humectants depending on the type and condition of the skin. From the physicochemical point of view, the formulations that provide the drug by passive diffusion must allow drug separation between the formulation and the skin and between the layers of the skin. This results in a concentration gradient through the skin layers which should be constant. The base of the dermal formulation significantly influences the solubility and thermodynamic activity of the active substance, which ultimately determines the distribution of the active substance from the substrate to the corneal layer of the skin. The dermal formulation should be designed in such a way that the concentration of the active substance in the composition is approximately equal to its maximum solubility while at the same time the solubility of the active substance in the substrate should be considerably lower when compared to the solubility of the active substance in the corneal layer of the skin. The solubility of the active substance in the base can be influenced by the composition of the base.