The development of personalized medicine requires new approaches to the development of dosage forms (DF), one such approach is rapid prototyping or in a different way the three-dimensional printing of tablets, plasters and other DF. Since the principle of individual dosing, the exact spatial arrangement of the pharmaceutical substance (PS), the possibility of using various geometric tablet forms to adjust the release rate, depending on the patient's need, is also possible in this approach, moreover, when creating a DF for the presented technology, it is possible to create and Quickly adjust the release profile according to the patient's requirements. A special impetus to the development of this technology was the recognition of the scalability of rapid prototyping and the release in 2016 in the US: with the approval of the FDA (Food and Drug Administration) 3D-printed orodispersible tablet Spritam® (levetiracetam). In this review we present methods of production of DF by the method of three-dimensional printing, such as the Theriform® process, stereolithography, extrusion, continuous inkjet printing, impregnated thread printing, microprojection, etc., classification of 3D printing types and features of each type of printing and equipment, on which the main technological process is produced. For the sake of clarity of the processes, the compositions and auxiliary substances used (AS), for example biodegradable polymers such as PLA, PLGA, etc., compositions of «ink» and powder substrates required for each type of process are given, as well as experimental data obtained from literature sources, curves release and technological properties of model samples. The possibilities demonstrated by the 3D printing of drugs to researchers and developers of the DF, in particular the rapid development and production of combinations of several PS with pulsatile, controlled, immediate or any other type of sequential release of the present FS in one DF are demonstrated. The evaluation of design features, advantages and disadvantages is carried out and the main components of the equipment for 3D DF printing are shown, the main attention is paid to such elements as printheads. it is their speed, mechanism of action and device that determines the type of rapid prototyping and the properties of the received DF. Conclusions about the prospects of this direction, in general, and of each technology separately, are evaluated, the advantages and disadvantages of the presented methods of DF production are estimated.

The results of the investigation on the excipients selection for "Ralitin" gel for oral administration containing Matricaria flowers extractives (sum of flavonoids, essential oil) are presented in the article. The extractive was obtained using previously developed ultrasonic extraction technology. Gel compositions of the extractive with sodium carboxymethyl cellulose (Na-CMC), carboxymethyl cellulose (CMC), agar, carbomer, xanthan gum, gum arabic, apple pectin and mixtures thereof (Na-CMC - gum arabic, CMC - gum arabic, apple pectin - agar, xanthan gum - gum arabic) were studied. Studies on the selection of flavouring agents (orange, raspberry, banana, coconut) and commercially available sweeteners containing sodium saccharinate, sodium cyclamate, fructose, stevioside, stevia leaf extract, inulin, sucralose, and erythritol were carried out. Use of citric acid in the gel compositions at various concentrations as an acidulant and a pH regulator was investigated. The appearance, pH 5% aqueous solution, stability at elevated temperature (40 °C), rheological characteristics: dynamic viscosity (at a given shear rate of 50 s^-1) and viscosity vs. shear rate (the shear rate measurement range was between 10 s^-1 and 200 s^-1 and vice versa) were evaluated for the gel compositions. The organoleptic characteristics of the gel compositions were evaluated using the profile method and the evaluation method with letter and numerical indexes by I. A. Egorov. The stability, aggregative stability, rheological characteristics, flavonoids release ("Dissolution" test), taste profile were determined for the developed gel composition for oral administration. The aggregative stability of "Ralitin" gel was studied under conditions of natural storage (20 ºС) and at elevated temperature (40 ºC). It was established that the value of the kinetic stability coefficient of the gel samples did not change during 6 months of storage and remained equal to 0, which allows considering the system as aggregatively stable. In examination of the sum of flavonoids release, it was found that about 90% of the total amount of flavonoids was released from "Ralitin" gel into the dissolution medium during the first 5 minutes. In studying stability of the gel during storage by the "accelerated aging" method, it was established that the obtained gel is stable during the entire experimental shelf life (2 years). "Ralitin" gel on the basis of Matricaria flowers extractive contains Na-CMC as a gelation agent, sorbic acid as a preservative, and flavouring agents - sucralose with inulin, banana flavour, and citric acid. Thus, the excipients selection for the formulation of "Ralitin" gel for oral administration has been carried out. Rheological characteristics, dissolution profile and organoleptic properties of the resulting gel are acceptable.

Studies of the osmotic activity of emoxypine and dalargine ophthalmic experimental gels samples based on various polymers and also studies of some marketed in Russia ophthalmic gels are presented in the article. Selection of the most promising for further study emoxypine and dalargine experimental gel compositions was based on the comparative study of Vidisic®, Solcoseryl®, Corneregel®, Oftagel® ophthalmic gels as well as 0,9% sodium chloride solution used as the standard of osmolality. Optimal values of osmotic activity have an experimental sample of an emoxypine ophthalmic gel containing Natrosol™ 250HHX at a concentration of 1%, as well as Oftagel® and Solcoseryl® gels.

The main objective of pharmaceutical technology is to maximize the use of «pharmaceutical factors» for ensuring the high quality of prepared medicines, which coincides with the strategic task of biopharmacy, which is to maximize the effectiveness of medicines and reducing to the maximum of their possible adverse effect on the body According to biopharmaceutical studies, dosage form substantially affect the validity of the included medicinal substances. In recent decades, a significant part of scientific research in the field of pharmacy is devoted to the creation of dosage forms based on targeted delivery systems of diagnostic and medicinal substances, among which liposomes have gained the greatest popularity. Liposomes are considered as promising delivery systems of drugs in the bloodstream because of its colloid properties, controlled size, surface characteristics, membranotropic and biocompatibility. However, the colloidal disperse systems are thermodynamically unstable, so the undoubted practical relevance in the development stage and the obtaining of liposomes presents a characterization and evaluation of stability of the resulting product. For this purpose, as a rule, use 3 core indicators - size of vesicles, polydispersity index and zeta-potential. The size of liposomes is one of the main indicators of the quality of liposomal preparation, which mainly depends on its component composition and technology. Dispersion of liposomes significantly affects the rate of elimination and distribution of the drug, the concentration in biological fluids and tissues, as well as determines the mechanism of cell internalization. Since in most macromolecular and nanodisperse systems molecules and particles are not the same, when describing the properties of systems, it is necessary to use the particle distribution functions according to their parameters, i.e. in the study of real systems to take into account their polydispersity, since monodisperse approximations can lead to incorrect conclusions about the properties of particles. The width of the particle size distribution is characterized by the polydispersity index. Zeta-potential is an important indicator of the surface charge of particles and a measure of electrostatic interaction (repulsion or attraction) between particles, as well as one of the main parameters affecting the stability of dispersed systems. Liposomes with high negative or positive zeta-potential repel each other and remain monodisperse and stable, and with low zeta-potential - are able to unite, aggregate and form unstable compounds. In addition, this parameter also allows you to predict the interaction of liposomes and cells.

Curcumin is a hydrophobic polyphenolic compound of natural origin. Curcumin has a wide range of pharmacological effects. Curcumin is inherently poorly absorbed when ingested and has low bioavailability, in part due to a low rate of absorption in the intestine and, in part, due to rapid metabolism (glucuronidation), which limits its clinical use. One of the important tasks is the development of effective forms of curcumin with the aim of increasing the bioavailability of this compound. This is achieved by including curcumin in such systems as liposomes, nanoparticles, micelles, etc., formation of complexes with cyclodextrins, and the use of bio-enhancers. In particular, the use of a complex of curcumin with piperine, a known inhibitor of the glucuronization process in the liver and intestine, increased the bioavailability of curcumin several times. Combination of curcumin with phospholipids due to its incorporation into lipophilic membranes, increased its maximum concentration in comparison with an individual curcumin. Curcumin in the form of nanoparticles had a pharmacological effect at a 15-fold lower concentration than conventional curcumin.

The process of extracting the Echinacea herbs (Echinacea Moench) has been developed with a series of water-alcohol solutions with an alcohol concentration of 70%, 40%, 20%. Extraction was carried out in the vacuum boiling mode with periodic pulsations of the vacuum. Such a regime provided high speed of the process and the possibility of extracting both lipophilic (chlorophyll derivatives, carotenoids) and hydrophilic (chicory acid and its derivatives) BAS. The kinetics of BAS extraction at three stages of maceration was studied: chicory acid is extracted by the polar extractant at all stages of extracting; the lipophilic components pass into the extraction at the stage of treatment with an alcoholconcentration of 70%. Method of micropreparative thin-layer chromatography with eluting and UV-analysis of the eluates was used to determine the groups of extractable BAS. A comparison of dry extracts obtained by water extraction, 24% alcohol extraction and extraction of a number of extractants with sequentially increasing polarity was made. It is established that the method of polyextraction allows to obtain a product containing the widest spectrum of BAS Echinacea.

The aim of the study on the development conditions for extraction of a series of three-part herbs, Bidens tripartita L., Solidago canadensis L. and Agrimonia eupatoria L. herbs in the technology of dry extracts. The influence of factors on the process of extraction of activety substances of a series of three-part herbs, Bidens tripartita L., Solidago canadensis L. and Agrimonia eupatoria L. have been studied. Features are studied and regularities of extraction of Bidenst ripartita L., Solidago canadensis L. and Agrimonia eupatoria L. herbs.

The article contains information about the fragment of the complex study on the introduction of Inula viscosa L. to the pharmaceutical practice. Inula viscosa L. is a plant growing in Syria. Its aqueous extraction and leaf powder is used in the Mediterranean traditional medicine for the treatment of dermatological pathologies. Based on the published scientific data on antimicrobial activity and the identified prospects for the production and use of preparations based on Inula viscosa L., a pharmacological and pharmacognostic study of leaf and herb raw materials is carried out using modern pharmacopoeial methods of research and standardization. The results of research of some pharmacognostic characteristics of new types of raw materials are presented for Inula viscosa L. leaves and herb. Quality indicators of raw materials are established: moisture content in leaves is not more than 5%, amount of herb is not more than 8%, ash content is not more than 11% in leaves and herb and ash, insoluble in 10% solution of hydrochloric acid is not more than 1% in both types of raw materials, content of substances extracted by water is about 32%. The technological characteristics of the crushed raw materials are studied: bulk density, bulk mass, absorption coefficients of solvents with different ethanol content, based on the values of which 70% ethanol is selected as extractant for extraction. 70% ethanol is able to extract a multicomponent target complex of substances including phenolic acids, flavonoids, tannins, sesquiterpenoids. The absorption coefficients of this extractant are 1,15 ml/g for herb and 1,22 ml/g for leaves. TLC is proposed for the identification of the plant raw materials and for the detection of flavonoids and phenolcarbonic acids (caffeic and chlorogenic acids) in aqueous and alcoholic extracts. There were identified two maxima of the absorption in the UV spectrum of the alcoholic extraction of Inula viscosa L. at wavelength 298 and 329 nm. It allows to assume the presence of phenolcarbonic acids and other phenolic substances including tanning substances and flavonoids in the extraction. The obtained absorption spectrum can serve as a specific characteristic for identification of medicinal plant material and extraction of Inula viscosa L. To develop the technology of extracts, the fractional composition of the Inula viscosa L. crushed raw material is determined. The majority of particles (about 44%) in the crushed herb of Inula viscosa L. have the size more than 2 mm, while the crushed leaves represent the fraction with majority of particles (about 45%) having size less than 2 mm but more than 1 mm. The obtained data is supposed to be used for the development of the draft normative documentation for Inula viscosa L. raw materials and for the development of technology for obtaining extraction preparations based on it.

In this article, experimental-industrial regulations for multi-component dosage forms for external use, including those containing nanoparticles, are presented. These forms are developed on the basis of the pharmaceutical composition "Novocomb", which has antiseptic, local anesthetic and prolonging action. Our preference was given to the following forms: external solution, ointment and napkin for external use. Evaluation of the obtained dosage forms was carried out for such indicators as authenticity, chromaticity, pH, content of active substances. An evaluation of antimicrobial activity and pharmacological action was performed, on the basis of which the principle of action of the composition on the burn injury model is presented.

With the help of thin-layer and high-performance liquid chromatography, the change in the composition of the reaction mass during the chlorination of salicylic acid was studied by three methods: molecular chlorine in acetic acid, sodium hypochlorite in an aqueous alkaline solution and oxidative chlorination with a mixture of hydrogen peroxide and hydrochloric acid in an acetic acid environment. It is shown that the most complete transformation of salicylic acid into 3,5-dichlorosalicylic acid is observed in the reaction with sodium hypochlorite, and the least complete - in the reaction of oxidative chlorination. It was found that the adverse reaction of the ipso-replacement of the carboxyl group with the formation of 2,4,6-trichlorophenol to the greatest extent occurs in chlorination of salicylic acid with gaseous chlorine in the acetic acid and with sodium hypochlorite in the aqueous alkaline medium. It is established that recrystallization technical 3,5-dichlorosalicylic acid of 50% aqueous 2-propanol to most effectively allows you to remove the admixture of 2,4,6-trichlorophenol, and to a lesser extent, admixture chlorosalicylic acids.

The results of development and validation of the method of vitamin E detrmination in microemulsion compositions suitable for its controlling in transdermal delivery systems and also for the incoming control of tocopherol acetate oil solutions presents in the article. The method is based on the vitamin E extraction from the microemulsion by a mixture of acetonitrile - ethyl acetate (80:20) and subsequent analysis by reversed-phase HPLC. The main validation characteristics of the method meet the eligibility criterias. The analytical area of the methodology was from 0.1 to 10.0 mg/g vitamin E concentration. The results of method approbation on transdermal delivery system laboratory samples on microemulsions based are presented.

This article covers the theoretical and practical basics of research of the robustness of chromatographic methods on the base of Plackett - Burman design. Step by step, with explanations and examples, the estimation of significant (potentially critical) factors as well as the estimation of permissible limits of the changes of factors and responses are considered. The assessment of the limits is important for the justification of the requirements to the suitability of a chromatographic system. Also, we suggest the recommendations for performing necessary calculations in Excel and for the assessment of robustness of chromatographic methods.

The antibacterial and antifungal activity of the products of the interaction of hydrazides of carboxyethyl alginic acid with 5-nitrofurfurol and β-(5-nitro-2-furyl)-acrolein was studied. The effect of analytical studies on the test-culture of Staphylococcus aureus, Escherichia coli and Candida albicans. The test compounds showed antibacterial action comparable to the furacilin and high antifungal effect. Samples of acylhydrazones β-(5-nitro-2-furyl)-acrolein have high fungicidal and fungistatic activity.

The global opioid crisis requires a paradigm shift in medical use of opioids, the development of methodology to reduce illicit drug use, and development of drug addiction treatment and antidotes. USA target program - HEAL Initiative is implemented under the scientific guidance of NIH with active participation of FDA, CDC and military medicine institutions. The situation in Russian Federation is characterized by a combination of high illegal consumption of dangerous opioids with an extreme shortage of potent analgesics, drugs for treatment addiction and overdose and rudimentary choice of drug formulations. There isn’t any development of innovative substances and preparations of strong analgesics and antidotes, but also a competent analysis of the subject area and vision of directions for the development. The data analysis shows need to replace some of traditionally used mostly natural and semi-synthetic narcotic analgesics (with low therapeutic index, unsatisfactory pharmacokinetics and severe side effects) to promising synthetic opioids and non-narcotic analgesics. Use of prodrugs, synergistic combinations, conjugates and co-drugs is justified. Prospective dosage forms of compounds and pharmaceutical preparations for development of wide range of improved therapeutics should combine: high analgesicactivity, high therapeutic index, minimum values of T_max and t_1/2k_e0, positive values of LogBB, distribution coefficient logD_7,4 in the interval from 1 to 3. This combination of key properties is necessary for effectiveness and safety of CNS-specific drugs and also allows development on their basis wide range of dosage forms (injectable and non-injectable drugs, fast-acting and prolonged drugs). First of all it is desirable to replace some obsolete injecting and oral preparations (especially with fast and uncontrolled release) to fast-acting transmucosal formulations with targeted pharmacokinetic properties. In order to analyze best practices, develop a strategy for highly effective controlled medicinal and veterinary drugs (analgesics, anesthetics, antidotes and other vital therapies) and coordinate theirdevelopment and production it is necessary to create competent management structure combining the tasks of provision of civilian population and personnel of national defense agencies of effective and safe drugs.

The review describes the first stage of phyto-pharmacological screening. It includes literature data analysis on promising species of medicinal plant raw materials, total extracts and individual substances of plant origin with pronounced pharmacological activity in disorders of fat and carbohydrate metabolism, incl. obesity, diabetes mellitus type 2, metabolic syndrome, and non-alcoholic fatty liver disease, confirmed in preclinical and/or clinical trials.

The high demand for insulin preparations by the population of the country makes it urgent to create domestic bioanalogues for the treatment of diabetes mellitus. The equivalency of the quality, safety and efficacy of the bioanalogue with the reference medicinal preparation registered in Russia is required by authority at the stage of preclinical studies. The aim of the study was to study the interaction of insulin substances of domestic production, including short and long-acting insulin with the insulin receptor in comparison with the reference substances registered in Russia by the surface plasmon resonance method. Comparing the interaction kinetics curves and calculated dissociation constants determined by the surface plasmon resonance method it was confirmed that there are no statistically significant differences between the potentially bioanalogical insulin substances Rosinsulin R, Rosinsulin Glargin and Rosinsulin Aspart (LLC ”Zavod Medsintez”, Russia) and the corresponding substances of registered in Russia medicines.

Accumulation of natural and artificial radionuclides and also biologically active agents in leaves of a plantain big, collected in the territory of the Voronezh region in the natural biogeocenoses which are influenced various anthropogenic influence is studied. Results of a research of the selected samples of leaves of a plantain big show, in general, ecologically safe condition of the studied medicinal vegetable raw materials. All samples meet requirements of the existing standard documentation on the maintenance of radionuclides and water-soluble polysaccharides. It is taped that the studied radionuclides in the concentration which is available in raw materials didn't exert impact on accumulation of water-soluble polysaccharides in leaves of a plantain big.

To study saponins from the roots of Achyranthes bidentata Blume (Amaranthaceae) were collected in Vietnam. Achyranthes bidentata is a tropical plant in the Amaranthaceae family, which is the most popularmedicinal plant in Asia. A complex of biologically active substances (BAS) was found in the roots of Achyranthes bidentata Blume that included saponins, ecdysteroids, polysaccharides, alkaloids, and coumarins. In this study, qualitative and quantitative analysis of saponins of Achyranthes roots was carried out. As a result of the studies, it was found that the roots contain at least three saponins predominantly triterpene group, which are derivatives of oleanolic acid. By spectrophotometric analysis of productsobtained as a result of the reaction of saponins with concentrated sulfuric acid, the quantity of the content of saponins was defined, equivalent to oleanolic acid is equaled 2,76±0,04%.

The results of comparative study of the mineral composition by the inductively coupled plasma-atomic emission spectrometry method of catnip herb (Nepeta cataria L.) which growing on the territory of the Leningrad Region and the Belgorod Region are presented. 16 and 18 elements were found in the herb from the Leningrad and Belgorod regions, respectively, with the maximum content of Ca, Mg, K, Fe and Al, which can be considered as the main mineral elements of this plant. The accumulation and distribution of Cu, Mg, Na is defined as an additional chemical marker for herb catnip. The results obtained allow us to consider the catnip herb as a potential source of mineral elements.

The known organic substances in yarrow causing its herbal effect are listed. A substantial influence of the territorial origin on the microelement composition of yarrow is shown. It is concluded that the content of microelements, including germanium, must be controlled using the modern methods of determination.

Comparative evaluation of glycyrrhizic acid content in licorice roots by methods of UV-spectrophotometry (GF RF XIII) and high-performance liquid chromatography (HPLC) was carried out. Sample preparation for HPLC method of quantitative determination of glycyrrhizic acid in samples of domestic production is developed. Small selectivity of UV-spectrophotometry at determination of glycyrrhizic acid is experimentally established and perspective of HPLC method for standardization of licorice raw materials is shown.

Embinin is a flavone C-glycoside from the aerial part of the milky white tangent (Iris lactea). Cardiotonic action was established earlier for the extract of Iris lactea. Identification of the active substance responsible for this type of biological activity seems to be an urgent task. The purpose of this study was to evaluate the cardiotropic effect and the toxicological profile of embinin. The acute toxicity of embinin was determined in accordance with GOST 32644-2014, the inotropic effect of embinin was evaluated in comparison with digoxin in the model of perfusion of the isolated rat heart by Langendorf, and also in vivo by echocardiographic study with calculation of the left ventricular shortening fraction and electrocardiogram analysis. The embinin in a dose of 2000 mg/kg didn’t cause the death of female rats. The substance has a pronounced inotropic effect. Establishment of a pronounced cardiotonic effect in the experiment and low toxicity, as well as a high probability of the presence of cardioprotective action of embinin, predicted using the PASS program, allow us to consider embinin as a promising molecule for further studies in cardiovascular disease.

The paper contains а results of the study of the pharmacokinetics, tolerability and safety of a new influenza drug Triazide in several dose regimens conducted on healthy volunteers. The convenient method for the determining the Triazide in blood plasma and urine by the HPLC have been proposed for the using in this study. There was no reliable statistical relationship between drug intake, undesirable clinical events and changes in laboratory parameters. A study of the pharmacokinetics have been showed that Triazide in the blood plasma was found on average after 0.5 hours, the curve of decrease in concentrations was two-phase, the half-life in the first phase was 1.5-4.0 hours. The maximum concentrations with increasing dose increased in direct proportion. With an increase in the daily dose, the maximum concentration was reached earlier. At the same time, no significant cumulation was observed with prolonged use. In the study, Triazide was well tolerated by all participants in all studied dose regimens. Preferred regimens that provide maintenance of effective and safe concentrations, appearances were 300 mg two and three times a day.

The recommendations of admissible corrections of the chromatographic conditions provided in chapter 2.2.46 of the European Pharmacopeia in the section "Adjustment of chromatographic conditions" are examined. Based on experience of the investigation of robustness of HPLC and UPLC methods and literary data, the article points out which of these recommendations are not suitable or have significant restrictions for the methods of impurities determination. An example that confirms some of the specified restrictions is given. For methods for determining impurities, it is recommended: to use admissible corrections of the chromatographic conditions from chapter 2.2.46 of the European Pharmacopeia, in section "Adjustment of chromatographic conditions" only in the absence of closely located or partially overlapping peaks of impurities not used for control of the resolution of chromatographic system on the chromatograms of the test solution of pharmaceutical substance / drug at the end of its shelf-life or on the chromatograms of the sample solutions after stress testing; an alternative condition is the absence of such peaks on the chromatograms of the solutions obtained under stress testing with the drug substance; to set admissible limits for the change (corrections) of the chromatographic conditions on the basis of the investigation of the robustness of the methods, and to include them, if necessary, in the methods.

The article contains information on the use by scientists of skills and abilities to conduct research in the field of patent science, to introduce the latest and progressive results of your developments into the production process. The presented aspects of the research work of the FGBNU VILAR in the field of intellectual property, allowing to make the results of scientific activity more relevant and significant.

The paper presents information about F.B. Schwabe and N. Zaklin, entrepreneurs of the late 19th and early 20th centuries who, through their labor and ingenuity, created the material and technical base that provided the development of various branches of natural science. Through their work they contributed to the development of medicine, pharmacy, chemistry, biology, geology, astronomy, etc. In addition to supply, they carried out certain educational functions. The business qualities and principles of organization of the enterprises led by them have not lost their relevance and are being applied at present.