Vol 73, No 6 (2024)

Introduction. Extraction dosage forms based on medicinal plant materials are very popular for medical use and must meet safety requirements. As part of the harmonization of pharmacopeial requirements, determining the total content of heavy metals in dry extracts is not enough. It is necessary to unify methods for determining heavy metals and arsenic in medicinal herbal preparations.

Objective: to determine the content of heavy metals and arsenic in dry extracts from raw materials of various morphological groups containing essential oils.

Material and methods. The objects of the study were dry extracts of calamus rhizomes, rhizomes with valerian roots, mint leaves and chamomile flowers obtained under industrial conditions. Sample preparation was carried out using microwave decomposition and ashing in a muffle furnace. The elemental composition was determined by inductively coupled plasma mass spectrometry.

Results. The content of 16 elements (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Mo, Cd, Sb, Hg, Pb) in the studied extracts was determined. Mercury was not detected in the samples, the concentrations of the 15 elements found were in the range of 0–250 mg/kg, and toxic elements (Pb, Cd, As, Hg) did not exceed 0.233 mg/kg. The largest quantities contained iron and manganese, and the smallest quantities contained chromium, arsenic, lead and cadmium. The maximum number of elements was contained in the studied samples of rhizome extract with valerian roots, the minimum – in the extract of calamus rhizomes. The morphological group of the feedstock and the specific features of the accumulation of elements can play a decisive role. The results of the study are consistent with the literature data. A comparative analysis of two methods for sample preparation of dry extracts showed that microwave decomposition in closed vessels is preferable, in which 24% more elements are quantified than after ashing in a muffle furnace. The possible intake of minerals into the human body when consuming an extract of rhizomes with valerian roots was calculated. It was established that the amount of elements did not exceed the upper permissible levels of daily intake, on the basis of which the studied extracts can be considered safe for medical use.

Introduction. The article is dedicated to modern principles of regulation and control of impurities in pharmaceutical products and active pharmaceutical substances, which is a crucial task for the pharmaceutical industry. The relevance of this research stems from the fact that the presence of impurities in pharmaceutical products can significantly affect their safety and efficacy, making the development of stringent control methods throughout the entire life cycle of a pharmaceutical product essential. Even small amounts of impurities can cause adverse effects or reduce the therapeutic value of drugs, as evidenced by historical examples.

The aim of the study is to analyze and systematize contemporary approaches to the detection and regulation of impurities in pharmaceutical products. The paper reviews current regulatory requirements, including guidelines from the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and regulatory documents of the Eurasian Economic Community, as well as national pharmacopeias of the Russian Federation, the United States of America, and the European Union.

Conclusion. Additionally, the article emphasizes the need for harmonization of standards and practices for impurity control, which is especially relevant in the context of the globalization of the pharmaceutical market. Harmonization not only enhances the safety and efficacy of pharmaceutical products but also improves patients' quality of life by reducing the risk of adverse effects associated with impurities. The article also explores prospects for further improvement of regulatory acts and the implementation of advanced technologies aimed at enhancing standardization and quality control in the pharmaceutical industry.

Introduction. Microbiological quality is one of the key criteria for active pharmaceutical ingredients. To ensure it, a set of preventive measures and various decontamination methods are used. A relatively new approach is ionizing radiation, characterized by high efficiency. However, according to the literature, during ionizing sterilization, a change in the chemical composition of the drug may occur, which requires studying the effect of the radiation factor on each individual compound.

Objective. To investigate the effect of ionizing radiation on the stereoisomeric composition of the dihydroquercetin (DHQ), a natural flavananol and a promising object for the development of chiral remedies.

Material and methods. The object of the study is a sample of DHQ exposed to ionizing radiation of 9.5 MeV (DHQ_rad), while the reference sample is a native substance of DHQ from the same manufacturer and batch (DHQ_ref). Analysis was conducted using polarimetry and reversed-phase HPLC with diode array and mass spectrometric detection.

Results. Taking into account the moisture content of the samples, the average values of the specific optical rotation for acetone solutions of DHQ_rad and DHQ_ref were 20.85±1.54° and 19.65±1.93°, respectively. Chromatograms showed two peaks with retention times of 10.18±0.03 and 11.63±0.01 min, which, based on UV and mass spectra profiles, were identified as trans- and cis-diastereomers of DHQ. The total content of flavananol in the analyzed samples was 93.25±0.01% for DHQ_rad and 94.92±0.01% for DHQ_ref, with the amount of the cis-isomer being 0.59±0.13% and 1.27±0.70%, respectively.

Conclusion. The study did not establish a significant effect of ionizing radiation on the specific optical rotation value and the stereoisomeric composition of the DHQ substance. The findings support the recommendation of this sterilization method for remedies containing the studied flavananol.

Introduction. The article provides information on the functional properties of various melanins and their biosynthesis, as well as natural sources of their production, the use of medicines and dietary supplements containing melanin in medical practice.

To do this, a systematic search was conducted in the databases: CyberLeninka, eLibrary, PubMed, SAGE Premier, Springer, Wiley Journals, over the past 10 years (2013–2023). As a result of the review, it was revealed that melanins are widespread in living organisms and are an important natural biomaterial. Melanins of microbial, fungal, animal and plant origin are known, they are divided into five types, of which the most studied are eumelanin, pheomelanin and neuromelanin.

A number of studies are presented that prove that melanins are characterized by a wide range of biological activity. They have photoprotective, radioprotective, antimutagenic, immunomodulatory stress-protective, geroprotective, antioxidant, detoxification and anti-inflammatory effects.

Information is provided on the possible use of melanin in the complex therapy of melanoma, Parkinson's disease and neurodegenerative diseases, to protect the skin and eyes from radiation damage, correct stress conditions and prevent infectious diseases during the epidemic season.

It has been shown that melanin chaga is widely used in domestic medicine in the form of medicines (Befungin) and dietary supplements. An important difference between them is the concentration of melanin, the method of its isolation and purification, as well as the manufacturing technology, which is demonstrated in the article. A biologically active additive with an additional source of β-glucans and polyphenols Amelan is considered, the main active component of which is melanin of fungal origin obtained by a method that increases the yield of melanin and improves its quality by increasing the concentration of its paramagnetic centers compared with melanin obtained without the specified pretreatment of fruit bodies.

Conclusion. The information presented in the article on melanins and their functional properties indicates the prospects of using melanins as a source for the production of medicines and biologically active additives.

Introduction. The ecosystem approach to the organization of business processes in the pharmaceutical market meets the prevailing trends, so the growth index of e-commerce in the retail sector of medicines for 5 years amounted to 1.87. The market distribution sector of medicines in the Russian Federation is characterized by a shift in corporate governance towards marketing cooperation based on aggregation electronic trading platforms (AETPS). Development of territorial pharmaceutical ecosystems (TFE) As a new integrative tool for managing the pharmaceutical development – production – distribution cycle, in order to achieve the target model of PHARMA 2030 at the territorial level, it requires the development of regulatory mechanisms for managing the supply of medicines.

Objective: characteristics of integration processes in the industrial, wholesale and retail sectors of the pharmaceutical market to assess the potential competitiveness of territorial pharmaceutical ecosystems.

Material and methods. The primary data for the analysis were: volumes of wholesale commodity residues of medicines produced in the Ural Federal District (461 registration certificates; proprietary Price and Distribution Test data for 230 trade names of LP (p<0.1)); EMIS data 2021–2022; Alpharm data 2021–2022; Datainsight 2022. In the course of the study, a structural analysis of the pharmaceutical market, a functional analysis of participants in the pharmaceutical product chain, and a marketing analysis were carried out.

Results. It was found that the dynamics of the AETP segment development corresponds to the outstripping growth of highly integrated platforms: the short-term growth index of 5-pl AETP (Uteca) is 164%, 4-pl (Eapteca) is 55%, 3pl-AETP (averaged) is 36.5%. The absence of formal mechanisms of regional protectionism for the sale of finished dosage forms of local manufacturers in the Ural Federal District has been revealed.

We have obtained the results of evaluating the effect of ecosystem integration of certain types of pharmaceutical market participants. For manufacturers of medicinal products, it was determined that the median coefficient of penetration of the local assortment of medicinal products into the pharmaceutical market in the context of ATX groups of level 2 is 0.67, which indicates a significant diversification of the assortment portfolio and the possibility of its aggregation without a barrier of internal competition. In the wholesale drugs sector, the potential for saving margins on medicines has been identified when implementing the scenario of localization of supplies in production regions in low and medium-low price ranges (30 – 550 rubles/unit), varying between 53–67%. It was found that the median share of regional distribution in the Ural Federal District (in packages) is 20.72%. It has been established that the Ural Federal District is one of the leaders in terms of the share of omnichannel consumers in the pharmaceutical market (63%), which is a significant incentive for the integration of organizations in the retail sector of the pharmaceutical market into the ecosystem 5pl platform.

Conclusion. Situational analysis of the morphology of cooperative interactions in the pharmaceutical market allowed us to identify the prerequisites for the formation of ecosystem-organized management structures in the pharmaceutical market system – territorial pharmaceutical ecosystems. We have systematized incentives for ecosystem determination of medicines supplies, and found that: an additional channel for the market distribution of the industrial range of medicicnes in the Urals is not associated with a barrier to internal competition of pharmaceutical plants; the inclusion of regional suppliers in TFE will allow to form additional competitiveness in the “buyer's market” in conditions of market dominance of federal suppliers; the omnichannel approach to the distribution of the retail range of TFE in pharmacy organizations has a high projected conversion rate. A detailed assessment of integration processes in certain sectors of the pharmaceutical market did not reveal critical barriers to the introduction of TFE.