Experimental Investigation of Immunomodulator Galavit^® Diffusion in a Model System

Abstract

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.

Aminodihydrophthalazinedione Sodium Transdermal Therapeutic System Specific Activity on an ExperimentalModel of Extensive Liver Resection

“…The first layer is a backing film used as the outermost layer of a transdermal system to protect the product during wear, the second line is a nonwoven material containing an emulsion composition with an immunomodulator and percutaneous carriers, and the third layer is an anti-adhesive film that is removed before use. The composition of the emulsion was published earlier [ 8 ].…”

“…At the first stage, a new dosage form of the immunomodulator was developed—the ADPS TTS, with the presence of percutaneous transfer of the drug substance proved in vitro [ 8 ]. In the second stage, the pharmacokinetic studies of the immunomodulator TTS were carried out [ 9 ].…”

“…Deionized water (Simplicity ® UV, Millipore, NJ, USA), 0.9% sodium chloride solution (ESCOM, Stavropol, Russia), sodium dodecyl sulfate (C 12 H 25 SO 4 Na, AppliChem Panreac, Barcelona, Spain), apricot kernel oil (oil with a similar fatty profile—3 to 10% palmitic acid (C 16 H 23 O 2 ), 0.5–4% stearic acid (C 17 H 35 COOH), 55 to 70% oleic acid (C 18 H 34 O 2 ), and 22 to 35% linoleic acid (C 18 H 32 O 2 ), max 1% linolenic acid (C 18 H 32 O 2 ) (Desert Whale Jojoba Company Ltd., Tucson, AZ, USA), α-tocopherol acetate (C 31 H 52 O, BASF SE, Ludwigshafen am Rhein, Germany), sodium docusate (C 20 H 37 NaO 7 S, Sigma, Saint Louis, MO, USA), Decaglyn PR-20 emulsifier ((C3H5O 2 ) n (C 18 H 32 O 2 ) m , Nikko Chemicals Co., Ltd., Tokyo, Japan) were used in the manufacturing of matrix-type laboratory samples of the aminodihydrophthalasindione sodium transdermal therapeutic system (“SELVIM”, Belgorod, Russia) with an emulsion delivery system [ 8 ]. As auxiliary materials of the TTS, the following were selected: elastic micro-sponge Foam tape 9773 (3M, Saint Paul, MN, USA), sorbing base PALV-01 (Palm Group of Companies LLC, Moscow, Russia), and Skotchpak 9730 film (3M, Saint Paul, USA).…”

“…The authors have developed a transdermal therapeutic system containing the ADPS synthetic immunomodulator [ 8 ]. Such a dosage form will make it possible to use this drug in various groups of patients who, for several reasons and/or contraindications, cannot use the existing dosage forms of ADPS.…”

Comparative analysis of pharmacokinetic parameters of transdermal and intramuscular administration of Galavit®

“…В связи с возрастанием в настоящее время интереса к применению иммуномодулятора Галавит ® при коронавирусной инфекции COVID-19 разработка и исследование новой лекарственной формы является перспективной задачей. Ранее авторами была разработана и исследована in vitro трансдермальная терапевтическая система [10,11], содержащая аминодигидрофталазиндион натрия. Результаты проведенных экспериментов доказали принципиальную возможность трансдермального переноса ЛВ, что позволило перейти к исследованию ТТС Галавит ® на животных in vivo.…”