Polymorphic Crystallization Design to Prevent the Degradation of the β-Lactam Structure of a Carbapenem

The cooling crystallization of carbapenem CS-023 was performed at 25 °C in an aqueous solution. Tetrahydrate crystals (form H) were obtained. Hydrate crystals are promising drugs, but there has been problems in manufacturing such crystals. During cooling crystallization, a dissolution process at a high temperature of 70 °C was utilized. The main problem in manufacturing was that the degradation rate of CS-023 at 70 °C was high, as expressed in the half-life period of 2.97 h. Poor solvent crystallization using ethanol was observed at 25 °C. Thus, a different polymorph (Form A) was obtained. Form A comprised CS-023, 5/2 ethanol, and 1/2 H2O. Form A, containing ethanol, is not suitable as a drug. Form A was then transformed to another polymorph of hydrate crystals or tetrahydrate Form H. Another hydrate polymorph, Form B, was obtained through the solid phase transformation of Form A and further transformed to the tetrahydrate Form H, at high humidity over 80% RH. This process, which proceeded at the low temperature of 25 °C, helped to prevent the degradation of CS-023, thereby avoiding wastage. Furthermore, the solid-phase transition could be controlled with vapor composition.

COMPARATIVE CHARACTERISTICS OF MEDICINAL PRODUCTS ASSORTMENT, MEDICAL DEVICES AND DIETARY SUPPLEMENTS BASED ON CHITOSAN DERIVATIVES REGISTERED IN THE REPUBLIC OF BELARUS, THE RUSSIAN FEDERATION, UKRAINE AND THE REPUBLIC OF KAZAHSTAN

The article presents the nomenclature of medicines, medical devices and dietary supplements based on chitosan derivatives registered in the Republic of Belarus and the neighboring countries. Comparative marketing research of the product groups studied has been carried out. Marketing parameters of this market sector have been established: the list and the structure of this segment by the drug form, manufacturing countries, pharmaceutical distributors and sources of origin. The assortment was analyzed in the specified regions according to the indicators: the number of names, pharmacological action, dosage form and the group of products in accordance with their registration. The coefficients of breadth, completeness and depth of assortment have been calculated. The expediency of studying pharmacological properties of chitosan derivatives further and the development of new original medicinal products based on them is shown.

A new indolocarbazole derivative in melanoma and carcinoma lung in vivo treatment

Objective The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods Female F1 hybrid mice (C57Bl/6 x DBA/2) and male and female linear mice C57BL/6 were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269.

Synthesis and characterization of isoniazid immobilized polylactide-co-glycolide nanoparticles

This article considers someaspects of synthesis and characterizationof polylactide-co-glycolide nanoparticles immobilized withthe antituberculous drug isoniazid. The influence of some synthesis parameters of nanoparticles (the ratio of drug substance:polymer and surfactant concentration) onproperties of the obtained nanosomal drug form of isoniazid has been studied. Optimal conditions for obtainingthenanoparticles with the best physicochemical parameters such as: particle size, polydispersity, conversion, etc. have been found. These nanoparticlescan be used asdrug carriers.The results revealed thata polymer: drug ratio of 1:1 and the use of 3% Twin 80 are necessaryto obtain stable emulsions of nanoparticles of polylactide-co-glycolide with satisfactory characteristics. Average size of the obtained particles was 196.4 nm,and the polydispersity value was 0.323. The aggregation stability of nanoparticles during 4 hours at temperatures of 4ºC and 20ºC has been evaluated. The morphology of the obtained nanoparticles has been studied.Analysis of nanoparticles was characterized by various instrumental methods includinggas chromatography and thermogravimetrytechniques. The resulting nanoparticles of polylactide-co-glycolide immobilized with isoniazid are stable in time andcanprolong the action of the drug. In vitrorelease of isoniazid from polylactide-co-glycolide nanoparticles hasbeen studied.

Cholesterol and its esters in the bile of rats in tetracyclineinduced hepatosis and under the using of milk phospholipids

The increase of disorders of the cholesterol metabolism and the bile formation determines the need of the search for possible substances correcting the cholesterol metabolism in the liver. It is found that, in laboratory rats with an experimental drug form of steatosis, the excretion of cholesterol and, especially, cholesterol esters to the bile ducts is inhibited, and their ratio in bile is significantly impaired. The use of bioadditive “FLP-MD” made on milk phospholipids has a corrective effect on the concentration of cholesterol and its esters in bile of rats with tetracycline-induced steatosis. This allows us to recommend bioadditive “FLP-MD” made on milk phospholipids to improve the cholesterol metabolism in patients with clinical cases of drug-induced liver damage.

Evaluation of allergenic properties and immunotoxicity tablet dosage form GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazin-3-carboxamide)

The study of allergenic properties and immunotoxic effects of the ready-to-use drug form of GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazin-3-carboxamide), compounds with high TSPO affinity and pronounced anxiolytic activity, was carried out. The study of allergenic properties and immunotoxicity of GML-1 was performed on male albino guinea pigs weighing 250-300 g and on male CBA, C57BL / 6, F1 hybrids (CBAxC57BL/6) mice. When assessing immunotoxicity, GML-1 was inject to mice per os for 14 days in doses of 2.2 mg / kg and 22 mg / kg. When studying the allergenicity, GML-1 was injected to albino guinea pigs in doses of 1 mg / kg and 10 mg / kg according to standard regimens of immunization. The results of the study of the immuno-toxicity and allergenicity of GML-1 allow us to conclude that the injection of tablet dosage form of GML-1 in the range of studied doses does not have an immunotoxic effect and allergenic properties.

Development and Validation of Dimeric Macrocyclic Tannin Assay Method in Dosage Forms

Introduction. Quantitative assessment of the active substance is necessary and perhaps the most significant part of the drug quality control. Validation of the analytical methods of quantitative assessment ensures their compliance with high requirements. The present study describes the development and validation of a spectrophotometry method for the quantitative evaluation of the active substance in the drug form of the national antitumor and antiangiogenic drug «Dimeric macrocyclic tannin (DMT) lyophilizate for solution for injection, 100 mg».Aim. The development and validation of the assay method for the standardization of «DMT lyophilizate for solution for injection, 100 mg».Materials and metods. The study used «DMT lyophilizate for solution for injection, 100 mg» and the active substance DMT. Method – spectrophotometry.Results and discussion. The methodof the quantitative assessment of the active substance in the DMT lyophilized drug by direct UV spectrophotometry was developed and the validation characteristics of the method were defined as a result of the study.Conclusion. The validation results showed that the assay method of DMT in the drug form has the appropriate accuracy, precision and linearity. The obtained results correspond to the approved criteria that allow the use of the developed methodology for evaluating the quality of the drug.

Current aspects of pathogenesis and prophylaxis of pelvic adhesions

Introduction. Adhesive process of the pelvic organs is a pressing issue for operative gynecology that does not allow to consider results of therapeutic and preventive measures as sufficient.Aim: to analyze published data regarding contemporary aspects of etiopathogenesis of the adhesive process in pelvic organs as well as methods of its prevention.Materials and Methods. The literature sources retrieved from electronic databases PubMed, Embase, Medline, Ovid HealthSTAR, Cochrane, Google Scholar, eLibrary, CyberLeninka as well as scientific articles published in peer-reviewed open access journals over the last 30 years, including basic research in the field have been analyzed. While searching, the following keywords and their combinations in Russian and English were used: "adhesive process of the pelvic organs", "pathogenesis of the adhesive process", "prevention of the adhesive process", "gynecology", "pelvic adhesions", "pathogenesis of adhesions", "аdhesion prophylaxis", "gynecology".Results. The current aspects of the etiology and pathogenesis for adhesive process have been summarized. Existing adhesion classifications are presented. The proposed methods for preventing formation of peritoneal adhesions are described exerting most prominent effectiveness as well as describing the properties and characteristics according to the application method, the composition of contained substances and drug form. A phenotype profile of peripheral blood and peritoneal fluid lymphocytes from patients with adhesive process remains debated.Conclusion. A need to further examine formation of peritoneal adhesions at molecular and cellular levels for developing a comprehensive pathogenetically substantiated method to prevent and treat adhesions of the pelvic organs is in demand.