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Introduction. The widespread use of immunomodulators in medical practice contributes to the development of their new dosage forms.Aim. The aim of this work is to develop a transdermal therapeutic system (TTS) Galavit® and to study a diffusion of the drug from it through the Strat-M membrane in vitro.Materials and methods. The medicinal substance was Galavit® in the form of a powder for the preparation of a solution for intramuscular administration («SELVIM», Russia). Saline solution, sodium dodecyl sulfate, apricot kernel oil, Decaglyn PR-20 and others were used as excipients. Heidolph DIAX900 dispersant (Germany) and ultrasonic homogenizer Heilscher UIS250V (Germany) were used to make the emulsion compositions. The delamination time and particle size of emulsion compositions were determined using the LUMiSizer dispersion analyzer (LUM, Germany). Diffusion studies of Galavit® from TTS through the Strat-M membrane (25 mm in diameter, Merck Millipore) were carried out on the Copley diffusion analyzer (UK). Quantitative determination of Galavit® was performed by spectrophotometry (UV-2600 Shimadzu, Japan) in the wavelength range 294–298 nm in model media.Results and discussion. The characteristic parameters of emulsion compositions were determined during the study: the particle size varied from 0.1 to 2 µm, the delamination time – from 9 to 95 min depending on the composition. The maximum yield of the drug from the TTS was 30 % through the membrane.Conclusion. The possibility of transdermal transfer of Galavit® from TTS is shown in model experiments.

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Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task

There are several approaches to modeling percutaneous diffusion of drugs and predicting its effectiveness in the development of new transdermal therapeutic systems (TTS): mathematical models, synthetic and biological test-systems. The aim of the work is to substantiate the need to combined use synthetic and biological test systems at the initial stages of the transdermal therapeutic systems development using the Galavit® immunomodulator TTS as an example. Six batches of laboratory samples of TTS were made with a different composition of excipients in emulsions. Transdermal therapeutic systems formulations were screened on the synthetic test-system represented by Strat-M membrane (Merck Millipore). Based on the results of the study, two formulations with the best data of the drugs amount passed into the receiving chamber of the Franz diffusion cell were selected. Amount of drugs in the form were amounted 30 %. The use of non-preserved rabbit skin was revealed significant differences in this indicator for TTS of these two compositions. The mass of drugs passing through the skin from the TTS Galavit® for 24 hours of application for the first emulsion was 58 – 71 % and was 39 – 50 % for the second. The biological test-system turned out to be more sensitive to the emulsion compositions. Thus, the combined use of synthetic and biological test-systems makes it possible to significantly reduce the complexity and costs of preclinical studies of new TTS.