# Somatotropin Penetration Testing from Formulations Applied Topically to the Skin
## 1 Introduction
Factors including enzymatic activity, blood supply and hydration decrease the passage of drugs, and the site of the skin to which the preparation is applied varies in SC thickness and lubrication. Drugs penetrate the mucous membranes most easily; less easily through the back (0.29 mg/cm\({}^{2}\)/h) and trunk (0.34 mg/cm\({}^{2}\)/h); and with most difficulty through the palms (1.14 mg/cm\({}^{2}\)/h) and the soles of the feet [17; 18]. Adequate moisturization of the skin, as a consequence of which corneocytes in the SC swell, makes for the easier diffusion of active substances [19]. An important group of gels used in pharmaceutics is hydrogels, usually composed of hydrophilic polymers, which under certain conditions and at a certain polymer concentration undergo gelation--that is, the binding of a solvent (a mixture of water and glycerol or propylene glycol) to a polymer network (cellulose derivatives, carbomers, poloxamers, starch) [20]. Hydrogels can be applied to skin, mucous membranes, wounds, and can also be inserted into body cavities. Hydrogels have many advantages, including that they do not leave an oily film on the skin, can be simply removed from skin with water, and are mucoadhesive. Their structure and compatibility with the aqueous environment make them very attractive, biocompatible drug carriers [21]. Thanks to their flexibility, porosity and high water content, hydrogels can be used as vehicles for numerous drug substances, including peptides and proteins (ACTH); the pore size can be kept under control by adjusting the cross-linking of the polymer. The water interface of hydrogels is able to stabilize cellular and compound drugs, including peptides, proteins, oligonucleotides and DNA [22; 23]. In their trial, [PERSON] et al. described the approval of a long-acting STH in pediatrics [24]. Daily therapy with frequent non-adherence and fluctuations in dose can affect the following treatment outcomes. A long-acting growth hormone analogue was developed that allowed for less frequent administration [24; 25]. In 2021, the FDA approved treatment by the once-weekly administration of the STH preparation lonapegsomatropin-tcgd, SKYTROFA(Ascendis Pharma, Denmark), for pediatric patients. SKYTROFA(r) is a long-acting pro-drug of human growth hormone. Using _E. Coli_ recombinant DNA technology, STH was produced and conjugated to methoxypolyethylene glycol (4 \(\times\) 10 DamPEG) using a patentedTransCon linker [26]. After the subcutaneous administration of lonapegsomatropin at a dose of 0.24 mg/kg/week in pediatrics, the mean observed half-life was 30.7 h [27]. The side-effect profile was comparable to STH administered daily, and indicators such as fasting glucose and hemoglobin in those receiving lonapegsomatropin were mostly within normal limits [28]. Due to the numerous inconveniences that accompany injectable drug application, this study attempts to formulate a much less invasive skin formulation containing the peptide substance STH. For skin formulations, it is important to ensure convenient application and effective therapeutic concentration of the active substance. The purpose of this project was to a make a formulation that would allow diffusion of the active substance from the substrate and have appropriate rheological and physicochemical properties. To this end, we planned to trace the permeation of the active substance from the obtained formulation through a natural membrane, such as pig skin. To compare the permeation process, the process was also carried out using an artificial membrane--a cellulose membrane. Since STH has a short half-life, efforts have been made to prepare hydrogel formulations with the addition of the transport protein ALB, which could prolong the permeation time, and thus, increase the therapeutic efficacy of STH.