# Somatotropin Penetration Testing from Formulations Applied Topically to the Skin
## 4 Discussion
The addition of MPR to the nanogel formulation resulted in a reduction in viscosity and, inversely, viscosity values increased together with Carbopol 940 concentration [52]. In this study, the prolonged permeation time of STH up to 24 h in the present test confirms the effect of ALB on the length of this process. STH penetrated from the MC hydrogel in 3 h through porcine skin from the formulation without ALB addition. The addition of ALB, added in each amount used in the formulations produced, prolonged the permeation process. At the same time, ALB at a concentration of 0.2% (STH-ALB 1:1) increased the amount of STH permeated by 14%. When testing the process of STH permeation through the cellulose membrane, a strong kinetics match was observed for all three models used. In the test of STH permeation through porcine skin, a slightly better fit was recorded for the first-order model, while the Higuchi and Korsmayer-Peppas models showed a very similar fit. This effect may result from the complexity of the hydrogel system--degradation mechanism, pore size, and the feature of drug substance. These models are dedicated to specific systems, have different assumptions and differ from each other. Due to the slightly higher values of the regression coefficients and the results obtained in previous tests of peptide substances, the permeation rate was determined based on the first-order model. Drug release and subsequent skin permeation, which followed first-order kinetics, is described by drug concentrations obtained from an _in vitro_ dissolution test plotted against time--In % of remaining drug to time. This relationship can refer to drug forms containing water-soluble substances encapsulated in a porous matrix, such as MC-based hydrogel. The average regression coefficients' R\({}^{2}\) was 0.9812. In a test of STH permeation through the skin, the regression coefficients for the Higuchi and Korsmayer-Peppas models were lower than those of the first-order model. The kinetics of the process of release and permeation of therapeutic substances vary greatly. This is influenced by many factors responsible for the form of the drug: the physicochemical nature of the excipients and therapeutic substances, as well as the drug form itself and its properties. The hydrogel used for the preparation of formulations with STH and ALB is hydrophilic in nature, and the therapeutic substances are water-soluble peptides, which can affect the process of release--especially their viscosity, swelling ability, as well as the ability of ALB to transport other substances and prolong their t\({}_{50\%}\). Due to the heterogeneous process of the degradation of polymeric matrices, characterized by different pore sizes, a differential fit of the kinetic models of the process of therapeutic substances' release and permeation is observed [53; 54; 55]. Unambiguous interpretation of the course of these processes is not entirely possible. The kinetics of active ingredient permeation from hydrogels is an extremely difficult issue, and there is no clear interpretation. The effect of ACTH amount on its penetration degree from topical formulations has been reported. It was found that the higher ACTH concentration, the lower the degree of its penetration through the skin [22]. Another study by [PERSON] et al. examined the effect of another protein, ALB, on the permeation of ACTH from topical hydrogels for skin application. They observed that both the concentration of ALB and the amount of ALB in relation to ACTH were significant. The 2% of ALB did not increase the amount of ACTH released over 24 h. A greater effect was observed at lower concentrations, i.e., 1.5% of ALB and 1.5% of ACTH (1:1). The degree of ACTH penetration was approximately 2.7 times higher (40.76 \(\pm\) 3.51%). ALB also increased the rate of ACTH permeation by approximately 1.4-fold (\(p<\) 0.05) [12]. The results of the permeation process through the artificial and natural membrane may indicate the influence of the membrane on the transport of active substances.