# Somatotropin Penetration Testing from Formulations Applied Topically to the Skin
## 1 Introduction  
Somatotropin (STH), known as growth hormone (GH), is a polypeptide produced by the somatotropic cells of the anterior lobe of the pituitary gland [1]. The hormone is secreted pulsatielly in response to the action of somatoliberin and somatostatin secreted from hypothalamic neurons [2]. STH consists of 191 amino acid residues with a molecular weight (\(M_{\text{av}}\)) of 22 kDa [1, 3]. The cycle of GH release is pulsatile, with the largest diurnal increase in GH secretion occurring shortly after the onset of sleep, and smaller pulses occurring at intervals throughout the day, several hours after eating a meal [4, 5]. The total daily GH production of approximately 0.5 mg is highest in childhood and adolescence, while it decreases with age [5]. GH and insulin-like growth factor (IGF-1) levels in the aged decrease by 30-60%. Its pulsatile secretion, which is the most important factor regulating IGF-1, results in a rapid time half-life of growth hormone, ranging from 17 to 45 min [2, 5, 6]. The production of biosynthetic GH allows for the treatment of people with its deficiency [7], in low-growth conditions in which GH deficiency is not found, such as [PERSON] syndrome, [PERSON] syndrome, [PERSON] syndrome, idiopathic low-growth syndrome and chronic renal failure. STH has also been used in diseases that cause a loss of muscle tissue, cachexia due to HIV, cystic fibrosis, inflammatory bowel disease and neurodegenerative disorders [8]. Registered preparations of STH come in the form of a solution and a powder and solvent for preparing a solution for injection. Human serum albumin (ALB) physiologically maintains the effective osmotic pressure of colloids in plasma, influences the integrity of the vascular endothelium, has antioxidant and anti-inflammatory effects, maintains acid-base equilibrium, and participates in thetransport, distribution and metabolism of various endogenous and exogenous substances. ALB can have a stabilizing effect on certain proteins [9]. ALB is composed of 585 amino acids [10]. It is a simple polypeptide with a \(M_{uv}\) of 66.5 kDa and has no prosthetic groups [9]. Currently, almost all available protein preparations (hormone treatment, enzymes, growth factor, coagulation factor, interferon) are administered at large doses at frequent intervals, which can result in dose fluctuations and patient neglect. At present, technologies make it possible to extend the half-life of proteins, which can prevent rapid degradation _in vivo_ by fusing with immunoglobulins or serum proteins (ALB) and conjugating with natural or synthetic polymers [11]. [PERSON] et al. [12] demonstrated the effect of the concentration of ALB on the timing and extent of corticotropin (ACTH) permeation from hydrogels. ALB caused a delay in penetration that was dependent on the ratio of ALB to ACTH. Apparently, this effect was seen at a 1:1 ratio of ALB and ACTH (1.5% ALB and 1.5% ACTH) [12]. Drugs used on the skin enter through the upper epidermis layer--the stratum corneum, which varies in thickness from 10 to 80 \(\upmu\)m (stratum corneum, SC)--or one of the appendages (hair follicles). Passage leads over subsequent layers, dermis and subcutaneous tissue, creating the potential for systemic distribution of the drug [13]. There are many therapeutics administered to the skin that exhibit both superficial and systemic effects [14; 15]. Transport through the stratum corneum occurs generally by passive diffusion. Permeation depends on the affinity of the compound to the lipid environment [13]. The epidermis, which comprises most of the skin, provides a barrier to both hydrophilic and lipophilic substances [16]. The permeation of active substances through the skin depends on their physicochemical properties--small, oval-shaped molecules with high concentrations in the formulation penetrate most easily [17]. Therapeutic substance diffusion is improved via the use of carriers or sorption promoters.