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

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

Formulation Designing Factors for Development of Repaglinide Transdermal Therapeutic System

Repaglinide, a blood-glucose-lowering drug, has a shorter half-life (~1 hour), low oral bioavailability (LOB) (~56 %) due to the first-pass metabolism, and required frequent dosing (Three to four times daily) to control blood glucose level. Repaglinide transdermal therapeutic system (TTS) was prepared to provide continuous drug delivery for a prolonged time. Designing factors for development are selection and optimization of product ingredients, optimization of drug load, types of TTS, matrix thickness, and optimization of drug delivery. During development, repaglinide TTS were evaluated for physicochemical characteristics and ex-vivo skin flux at different stages. Based on the pre-formulation study data, Durotak 87-2516® was selected as a pressure-sensitive adhesive. Different formulations of a drug in adhesive matrix and reservoir type repaglinide TTS were evaluated for ex-vivo skin permeation (flux) study. The skin flux results show that sandwiched reservoir type repaglinide TTS can provide average cumulative drug permeation and flux rate of 379.75 ± 47.89 μg/cm2 and 4.62 ± 1.00 μg/cm2/hr respectively for sustain drug delivery over the time of 72 hours. Developed sandwiched reservoir type repaglinide TTS has the potential to sustain delivery of drug for 72 hours, which reduce frequent dosing and thereby improve patient compliance.

Comparative evaluation of the effectiveness of the transdermal therapeutic system with fentanil and gabapentine in head pain therapy

The study was conducted to comparatively evaluate the effectiveness a transdermal therapeutic system with fentanyl and gabapentin in the treatment of headache in patients with non-traumatic subarachnoid hemorrhage. When assessing the intensity of headache in patients, it was found that with severe pain immediately after endovascular occlusion, the use of transdermal fentanyl with dexketoprofen or paracetamol is most acceptable, and the combination of gabapentin with dexketoprofen / paracetamol is better in case of headache in a more delayed period.