Permeation of albumin through the skin depending on its concentration and the substrate used in simulated conditions in vivo.

OBJECTIVE: Many drugs applied to the skin with a systemic effect do not have a therapeutic effect, due to the barrier posed by the complex structure of the skin. To counteract this, absorption promoters are often added to the drug formulation. The use of albumin as an effective drug carrier is increasingly being addressed. Albumin, a natural, non-toxic polymer, can target drugs to specific cells and extend their biological half-life. This study was designed to trace the permeation of albumin after topical administration to the skin as a potential carrier of therapeutic substances. MATERIALS AND METHODS: Four dermal formulations based on different polymers were prepared: methyl cellulose, sodium alginate, hypromellose and chitosan with methyl cellulose, obtaining final concentrations of albumin of 2%, 1.5% and 1%. The permeation of albumin through the skin was examined under simulated in vivo conditions. RESULTS: Most albumin permeated from the methylcellulose-based hydrogel. Depending on the concentration of albumin, permeation profiles were plotted and permeation rate constant and AUC(0-24 h) were calculated. CONCLUSION: Methylcellulose was the optimal polymer for albumin release, whereas hypromellose was the least favorable. The concentration of albumin influences the amount and rate of permeation of this protein. The optimal concentration was 10 mg/g, from which the most albumin penetrated and the fastest. Human skin appeared to be more permeable to albumin than pig skin. However, the similar permeation profile through both membranes successfully allows the use of pig skin to track and evaluate the permeation of therapeutic substances with systemic effects.

Preparation of Sterile Raw Material - Chicken Eggshells in the Process of their Transformation into Selected Calcium Salts.

BACKGROUND: The chicken eggshells and their subcrustal membranes are a valuable source of calcium, but they are not further processed but disposed of as waste from the food industry. Chicken eggshells have high content (>95%) of calcium carbonate. Some properties suggest that eggshells may be a promising alternative to the present calcium sources used in the pharmaceutical industry. METHODS: The effect of roasting chicken eggshells with a selected organic acid (citric or fumaric or lactic acid) on microbiological purity, including the presence of fungi and bacteria Salmonella spp., Staphylococcus aureus, Escherichia coli of obtained calcium salts, was investigated. In this study, chicken eggshells were subjected to chemical reactions with organic acids (citric, fumaric or lactic acid) at two different calcium-acid molar ratios (1:1 or 1:3) and the mixture was heat-treated for 1 or 3 hours at a temperature of 100°C or 120°C. RESULTS AND DISCUSSION: It was found that lactic acid was 100% effective against fungi, and the remaining citric and fumaric acids were -50% (regardless of the other examined conditions). The type of acid used has a significant effect on fungal growth inhibition (p<0.05). Fumaric acid and lactic acid will be nearly 100% effective against bacteria (100% fumaric acid and 97% lactic acid effectiveness), regardless of other factors. CONCLUSION: Lactic acid is the most effective against pathogenic flora - fungi and bacteria. The transformation of chicken eggshells into calcium lactate can provide us with sterile calcium salt, free of 100% fungi and 97% of all bacteria.

Influence of Concentration on Release and Permeation Process of Model Peptide Substance-Corticotropin-From Semisolid Formulations.

The transdermal route of administration of drug substances allows clinicians to obtain a therapeutic effect bypassing the gastrointestinal tract, where the active substance could be inactivated. The hormonal substance used in the study-corticotropin (ACTH)-shows systemic effects. Therefore, the study of the effect of the type of ointment base and drug concentration on the release rate and also permeation rate in in vivo simulated conditions may be a valuable source of information for clinical trials to effectively optimize corticotropin treatment. This goal was achieved by preparation ointment formulation selecting the appropriate ointment base and determining the effect of ACTH concentration on the release and permeation studies of the ACTH. Semi-solid preparations containing ACTH were prepared using Unguator CITO e/s. The release study of ACTH was tested using a modified USP apparatus 2 with Enhancer cells. The permeation study was conducted with vertical Franz cells. Rheograms of hydrogels were made with the use of a universal rotational rheometer. The dependence of the amount of released and permeated hormone on the ointment concentration was found. Based on the test of ACTH release from semi-solid formulations and evaluation of rheological parameters, it was found that glycerol ointment is the most favourable base for ACTH. The ACTH release and permeation process depends on both viscosity and ACTH concentration. The higher the hormone concentration, the higher the amount of released ACTH but it reduces the amount of ACTH penetrating through porcine skin.

Development and Study of Semi-Solid Preparations Containing the Model Substance Corticotropin (ACTH): Convenience Application in Neurodegenerative Diseases.

Corticotropin (ACTH, previously an adrenocorticotropic hormone) is used in the diagnosis and treatment of pituitary gland disorders, adrenal cortex disorders, and other diseases, including autoimmune polymyositis, systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. So far, the ointment dosage form containing ACTH for use on the skin is unknown. Therefore, it seems appropriate to develop a semi-solid formulation with corticotropin. Emulsion ointments were prepared using an Unguator based on the cream base Lekobaza® containing corticotropin in different concentrations, and then the physical and chemical parameters of the ointment formulations, such as pH, spreadability, rheological properties, and texture analysis, were evaluated. In addition, a USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the selected formulations. All the ointments obtained were characterized by good spreadability and viscosity. An analysis of the ointment texture was performed and the dependence of the tested parameters on the ACTH content in the ointment was demonstrated. Examination of the structure of the ointment showed that a high concentration of ACTH increases the hardness and adhesiveness of the ointment. In turn, it adversely affects the cohesiveness and elasticity of the ointments tested. The results of the release study showed that ACTH is released the fastest from the formulation with the lowest concentration, while the slowest from the ointment with the highest concentration of ACTH.

Penetration of model hormones through the pericardium in simulated conditions in vivo.

The process of penetration of selected protein-peptide substances including insulin (INS), corticotropin (ACTH), prolactin (PRL) and albumin (reference protein) through the model membrane - pig pericardium was traced. These substances show a wide spectrum of therapeutic effects and diverse physicochemical properties (molecular weight, pI). The model substances penetrated the pericardium in simulated in vivo conditions from 1.0 mg / ml solutions. Based on the results obtained, pharmacokinetic parameters of the permeation process were determined - permeation rate (k), half-life (t50%) and their pharmaceutical availability (AUC [0-24 h]). All tested model substances penetrate the pericardium to different degrees. Within 24 h, they penetrate from 16.8% of albumin to 98.9% of insulin. Corticotropin penetrates 43.8% and PRL 34.2%. The highest availability is achieved with insulin, followed by ACTH, PRL and the lowest content of albumin. The results obtained suggest that the higher molecular weight of model protein-peptide substances, the lower the pericardial penetration (R2 = - 0.700) and availability (R2 = - 0.600), and the longer the half-life (R2 = 0.948).

Effectiveness of absorption and passage through the small intestine, as a model of oral prolactin administration.

The process of absorption and permeation of PRL through the small intestine of 1-day-old piglet from the different compositions of solutions prepared for oral administration was investigated. This was achieved by determining the effect of hormone concentration (0.25 mg / ml or 0.5 mg / ml or 0.75 mg / ml), the concentration of stabilizing substances - trehalose (6 mg / ml or 12 mg / ml or 18 mg / ml) and mannitol (6 mg / ml or 12 mg / ml or 18 mg / ml) and the pH of the solution (2.5 or 3.0 or 3.5) on the degree of absorption and permeation of the PRL. The conditions for the absorption and penetration of PRL from solutions of various compositions for oral administration through the natural membrane (small intestine of the 1-day-old sucking piglet) in the in vivo conditions were simulated. The studies used an in vivo model in which the enzymatic profile in the body is not yet fully developed (no pepsin). It was found that in the studied range the absorption of PRL in the small intestine of the 1-day-old sucking piglet is significantly related to the concentration of the hormone and trehalose in the solution from which it is absorbed. In contrast, all factors studied (hormone concentration, trehalose and mannitol concentration, pH value of the solution) influence the process of penetration of the PRL in the studied range. It was also found that the hormone concentration significantly influences the rate of its absorption and permeation (the fastest occurs at a concentration of 0.5 mg/mL). The results suggest possibility of oral prolactin administration in order to ensure proper growth, development and increase the resistance and survival of sucking piglets.

New Sources of Calcium (Chicken Eggshells, Chelates) - Preparation of Raw Material and Tablets.

BACKGROUND: There are many calcium supplements available in the market, especially those containing calcium in the form of carbonate, which unfortunately is not absorbed by the body to a sufficient degree. METHOD: Therefore, an attempt was made to prepare new sources of calcium, consuming the chicken eggshells as natural raw materials, which were used in preparation of tablets containing calcium carbonate and calcium citrate as well as tablets with calcium carbonate and calcium bisglycinate. The influence of raw material properties on the pharmaceutical availability of calcium from the obtained tablets was investigated. RESULTS: Based on the obtained calcium release profiles from the prepared tablets, it was found that the optimal source of calcium is a preparation containing calcium from chicken eggshells. It was found that both chicken eggshells and calcium bisglycinate (chelate) may be new, prospective sources of calcium. Calcium citrate prepared using eggshells as starting materials and bisglycinate is completely released within no more than 150 minutes. CONCLUSION: In turn, calcium carbonate added to calcium bisglycinate statistically significantly prolonges the release of calcium ions to 4 hours.