Requirements Of Pharmacopoeia Research Articles

Hygienic characteristics of ethanol for preventive use in skin antiseptics

Aim – to study the ethyl alcohol 70% of the Lux brand in respect to its chemical and analytical quality, toxicological safety, microbial effectiveness and to assess its use in skin antiseptics. Material and methods. The studies were performed using organoleptic, physical, chemical, toxicological and microbial analysis in accordance with standard modern methods. Results. Ethyl alcohol 70% has chemical, analytical and microbial quality indicators that meet the requirements of the State Pharmacopeia of the Republic of Belarus. According to toxicological indicators, it belongs to class IV – lowhazard substances, with no irritating effect, which corresponds to the regulatory toxicological indicators of the safety of skin antiseptics. During the primary epicutaneous application on volunteers, it does not cause subjective and objective symptoms of sensitization; it belongs to substances that do not have an irritating effect and sensitizing ability. Standard test cultures and clinical strains of microorganisms are highly sensitive to ethyl alcohol 70% in a qualitative suspension test tube and micromethod without protein load and moderately sensitive in the diskdiffusion method with an exposure of 1 min. In relation to these microorganisms, the antimicrobial activity of ethyl alcohol 70% is above 99.999% and a reduction factor above 5 lg at exposure of 1 min in a quantitative suspension method without a protein load. Ethyl alcohol 70% is also characterized by a high efficiency of normal skin disinfection and E.coli contaminated skin of volunteers over 99% and a reduction factor above 2 lg and 4 lg, respectively. Conclusion. Ethyl alcohol 70% of the brand "Lux" is a highquality, toxicologically safe and microbial effective drug. It can be recommended for skin antisepsis of the injection field (class A), as well as hygienic hand antisepsis (class B) and antiseptic sanitization of the skin in the Republic of Belarus and Russian Federation.

Exploiting specific properties of squid pens for the preparation of oligochitosan hydrochloride

Herein, we describe in first the application of squid pens for the preparation of pharmaceutical-grade oligochitosan hydrochloride with the physicochemical characteristics corresponding with the requirements of the European Pharmacopoeia. It is shown that the use of specific properties of squid pens as a source of parent chitosan allows preparing the product with a high yield at relatively moderate process conditions used for squid pens treatments and chitosan depolymerization.

Long-term oral administration of Kelisha capsule does not cause hepatorenal toxicity in rats

Ethnopharmacological relevanceKelisha capsules (KLS) are often used to treat acute diarrhoea, bacillary dysentery, heat stroke, and other diseases. One of its components, Asarum, contains aristolochic acid I which is both nephrotoxic and carcinogenic. However, the aristolochic acid (AA) content in KLS and its toxicity remain unclear. Aim of the studyThe aims of this study were to quantitatively determine the contents of five aristolochic acid analogues (AAAs) in Asarum and KLS, and systematically evaluate the in vivo toxicity of KLS in rats. Materials and methodsUltra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the content of the five AAAs in Asarum and KLS. Sprague–Dawley rats were administered KLS at 0, 0.75, 1.5, and 3.0 g/kg respectively, and then sacrificed after 4 weeks of administration or after an additional 2 weeks of recovery. The endpoints assessed included body weight measurements, serum biochemistry and haematology indices, and clinical and histopathological observations. ResultsThe AAAs content in Asarum sieboldii Miq. (HB-ESBJ) were much lower than those of the other Asarums. The contents of AA I, AA IVa, and aristolactam I in KLS were in the ranges of 0.03-0.06 μg/g, 1.89-2.16 μg/g, and 0.55-1.60 μg/g, respectively, whereas AA II and AA IIIa were not detected. None of the rats showed symptoms of toxic reactions and KLS was well tolerated throughout the study. Compared to the control group, the activated partial thromboplastin time values of rats in the 1.5 and 3.0 g/kg groups significantly reduced after administration (P < 0.05). In addition, the serum triglycerides of male rats in the 0.75 and 1.5 g/kg groups after administration, and the 0.75, 1.5, 3.0 g/kg groups after recovery were significantly decreased (P < 0.01 or P < 0.001). No significant drug-related toxicological changes were observed in other serum biochemical indices, haematology, or histopathology. ConclusionsThe AA I content in KLS met the limit requirements (<0.001%) of the Chinese Pharmacopoeia. Therefore, it is safe to use KLS in the short-term. However, for safety considerations, attention should be paid to the effects of long-term KLS administration on coagulation function and triglyceride metabolism.

Research for the selection of taste corrigents, filter materials and primary packaging for oral solution with magnesium salts

The aim. Theoretically and experimentally, justify the choice of excipients for a combined oral solution with organic magnesium salts. Determine the compatibility of filter materials of three types. Select single-dose primary packaging for the developed oral solution and confirm its suitability during the relevant studies. Materials and methods. Organoleptic, physicochemical, and pharmaco-technological methods were used in the investigation. All methods meet the requirements of the State Pharmacopoeia of Ukraine and the European Pharmacopoeia. Organoleptic methods indicated the taste of the medicinal speciality behind the methods of O.I. Tentsova and I.A. Egorov. Physicochemical methods were used to determine pH, colour, density, and quantitative amount of active pharmaceutical ingredients. Pharmaco-technological methods were used to determine the properties of filter materials and primary packaging. Results. A sweetener and a flavouring agent for an oral solution with magnesium salts were selected based on the research. Saccharin sodium was selected as a sweetener in the amount of 0.15 %. «Cherry» in the amount of 0.4 % and «caramel» in the amount of 0.2 % were selected as flavouring agents. As a result of experiments, the suitability of filter materials made of сapron, nylon and polyethersulfone was proven. This is determined by the constancy of the main quality indicators of the drug 24, 48 and 72 hours after filtration. The suitability of the single-dose primary packaging in the process of storing the oral solution has been studied and proven. In the work, polymer ampoules of the «Moplen EP 2S 12 B» brand and the «Purell HP 371P» brand were used. The conducted research allows us to create a competitive domestic drug that will be technologically simple and convenient in administration and will also be distinguished by relatively low raw material costs and production. Conclusions. Based on theoretical and experimental studies, auxiliary substances, such as sweeteners and flavouring agents, were selected for the combined magnesium-containing drug. The suitability of filter materials for the combined oral solution was investigated and confirmed. The suitability of single-dose primary packaging of two types was selected and experimentally proven

Comparison of diterpenoid contents and dissolution profiles of selected Andrographis paniculata crude and extract capsules.

Andrographis paniculata (AP) has been approved by the Thai government for the treatment of mild cases of COVID-19 patients. Increasing use of AP products requires quality control to ensure efficacy and safety. At present, there is no requirement for dissolution test of AP products in the Thai Herbal Pharmacopoeia (THP). This work aimed to examine the contents and dissolution profiles of active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3), neoandrographolide (AP4), and 14-deoxyandrographolide (AP6) in AP capsules available in Thai markets. Four extract products (EXT. A-D) and three crude powder products (CRD. A-C) were tested for contents by using HPLC-DAD. Dissolution profiles of four diterpenoids were investigated in different media (pH 1.2, 4.5, 6.8, and 0.01 N HCl + SLS) with apparatus II (paddle type). The AP1 contents were 1.99%-2.90% w/w for crude capsules and 2.84%-16.27% w/w for extract capsules. In the dissolution test, the dissolution percentages of four diterpenoids from crude capsules were higher than those from extract capsules except EXT. A. AP1 in most extract products (EXT. B, C, D) was dissolved in all dissolution media at a lower percentage than the other three diterpenoids. EXT. A (aqueous extract) was the only extract capsule showing the amounts of all diterpenoids dissolved in all media >80% in 45 min. The study demonstrated that AP1 content in AP products complied with the acceptance criteria in the THP (80%-120%), and the weight variation also met the United States Pharmacopeia (USP) requirements. However, different dissolution profiles of AP products may lead to different bioavailability of diterpenoids and further affect their efficacy.

Variation in the composition of the essential oil of commercial Artemisia absinthium L. herb samples from different countries

Wormwood (Artemisia absinthium L., Asteraceae) is an aromatic bitter herb that contains bitter-tasting metabolites and essential oil. The composition and biological effects of A. absinthium essential oil have been widely studied. However, the data on the content of the individual components vary significantly. The aim. The aim of the study was to research the compositions of essential oils from A. absinthium herb, which are on the market in various European countries and determine difference in their compositions, possible chemotypes, and compliance of the essential oil samples with the European Pharmacopeia requirements. Materials and Methods. The composition of 16 essential oil samples of A. absinthium herb from different countries was investigated using the gas chromatography method. Samples were obtained from retail pharmacies in 14 different countries. Research results. A total of 41 compounds were identified in the studied A. absinthium essential oils. In all the samples, monoterpenes and monoterpenoids dominate (28.0-92.2 %), much less sesquiterpenes and sesquiterpenoids (0-18.9 %). The dominant components among the identified ones were sabinene (traces(tr.)-21,2 %), myrcene (0.1-25.6 %), p-cymene (0.2-6.5 %), 1,8-cineole (0.1-18.0 %), artemisia ketone (tr.-14.9 %), linalool (tr.-10.8 %), β-thujone (0.1-38.7 %), (E)-epoxyocymene (tr.-59.7 %), (E)-verbenol (tr.-7.9 %), borneol (tr.-11.7 %), (E)-sabinyl acetate (tr.-70.5 %), neryl butyrate (0-13.9 %), spathulenol (tr.-9.2 %), caryophyllene oxide (tr.-7.3 %). Both “pure”-chemotypes and “mixed”-chemotypes of A. absinthium have been defined. Conclusions. Two”pure”-chemotype consist of 70.5 % (E)-sabinyl acetate and 59,2 % (E)-epoxyocymene, respectively. Also, eleven "mixed"-chemotypes of A. absinthium essential oils have been defined. Some correlations were established between the content of terpenes in the A. absinthium essential oils

Development of composition, technology and determination of quality indicators of medicinal films with etoricoxib

According to the Strategy for the Development of the Pharmaceutical industry until 2030, the development of new domestic medicines is one of the urgent tasks to ensure sustainable socio-economic development of the Russian Federation. In this regard, we have developed the composition and technology of a drug in the dosage form of a “Film”, dispersed in the oral cavity, with a nonsteroidal anti-inflammatory agent of selective action – etoricoxib. The choice of this dosage form is due to its advantages over other dosage forms, such as high bioavailability, no need to wash down the films with water and swallow, the prevention of the development of undesirable adverse reactions from the gastrointestinal tract.&#x0D; The purpose of the study was to verify the compliance of the manufactured model samples of films with etoricoxib with the requirements of the State Pharmacopoeia of the current edition. The article presents data on the development of the optimal composition of films and the method of selecting the concentration of preservative, the technology for producing films, as well as describes the processes and results of tests conducted to assess the quality of films according to some regulated indicators in accordance with the GPA “Films”, such as description, film dimensions, pH of the solution, uniformity of mass, microbiological purity.&#x0D; The results of the scientific work showed that the developed drug with etoricoxib meets the requirements of the General Pharmacopoeia Monograph “Films” for the quality indicators studied.

An Improved HPLC Separation Method for TSPO Radioligand [11C]ER176 Clinical Production.

Mitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi-preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5-9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.

A comparative analysis of compounding aqueous extracts from the medicinal plant raw material in accordance with the requirements of the regulatory legal acts of Ukraine and the European Union

In the world pharmaceutical practice, there are significant differences regarding the requirements for the technological parameters of aqueous extracts from medicinal plant raw materials.&#x0D; Aim. To conduct a comparative analysis of the requirements of regulatory documents of Ukraine, the European Union and Poland regarding the compounding of water extracts from medicinal plant raw materials.&#x0D; Materials and methods. Comparative analysis was carried out using systemic and structural-logical analysis. The object of research was normative legal acts regulating medicines compounding in Ukraine, European Pharmacopoeia (EP) XI ed., European Medicines Agency (EMA), Pharmacopoeia of Poland (PP) VI and IX ed., textbook "Farmacja stosowana, Technologia formaci leku; podręcznik dla studentów farmacji" and others.&#x0D; Results and discussion. As a result of the analysis, a few distinctive features in the technology of water extracts from medicinal plant raw materials were revealed compared to the requirements of the EU and Poland. According to the requirements of European Pharmacopoeia and the European Medicines Agency, aqueous extracts from medicinal plant raw materials, so-called herbal teas, are prepared with the methods of maceration, infusion and decoction. Macerates are prepared from mucilaginous medicinal plant raw materials with the method of cold infusion at room temperature for 30 minutes. Infusions are usually prepared from delicate parts of the plant, while medicinal plant raw materials are poured with hot water with an initial temperature of 90-100 ºС and infused by gradually cooling the extract at room temperature for 5-15 minutes. Decoctions are usually prepared from roots, rhizomes and bark by boiling medicinal plant raw materials in a boiling water bath for 15-30 minutes, while the raw materials are initially poured with an extractant at room temperature, and after boiling, the extract is immediately filtered.&#x0D; The compounding peculiarities of water extracts from medicinal plant raw materials in Poland are as follows: the ratio of medicinal plant raw materials to the extractant with weak biologically active substances is 1:10, with mucus-containing medicinal plant raw materials – 1:20; for medicinal plant raw materials with cardiac glycosides and alkaloids – 1:100; water extracts are prepared by mass, while water absorption coefficients or consumption coefficients are not taken into account; for acidification, 0.5 g of citric acid per 100 g of extractant is added to extracts from alkaloid-containing raw materials; macerates are prepared from mucilage-containing raw materials only by the cold infusion method (for example, flax seed macerate); infusions are prepared only from medicinal plant raw materials containing cardiac glycosides (Lily of the Valley herb, Adonis vernalis herb), where raw materials are poured with boiling water, infused in a water bath for 15 minutes and cooled at room temperature for 15 minutes; decoctions are always prepared from other types of medicinal plant raw materials, where the raw materials are poured with an extractant at room temperature, heated and boiled in a boiling water bath for 30 minutes, filtered without cooling.&#x0D; Conclusions. A comparative analysis of the technological parameters of water extracts compounding from medicinal plant raw materials in accordance with the requirements of regulatory documents of Ukraine, the European Union and the Republic of Poland was carried out. A number of differences have been established, particularly in the methods of recipes prescribing, features of calculations, in the ratio of medicinal plant raw materials to the extractant, temperature regimes, extraction time, medium pH, the concepts of the processes of maceration, infusion and decoction. It was found that compared to domestic regulations, the technological process in the EU and Poland is optimized in terms of time, energy and in some cases, raw material expenditure. The obtained results have a practical importance, as they are the basis for further scientific research on the substantiation of the influence of technological factors on the quantitative content of the main groups of biological active substances in the compounded water extracts.

Certification of a pharmacopoeial reference standard for potency testing of recombinant interferon α-2b

SCIENTIFIC RELEVANCE. Potency testing of recombinant interferons requires a reference standard. The availability of International Standards (ISs) that are commonly used to assess the quality of recombinant interferons is currently limited. Therefore, the quality of interferons should be assessed using pharmacopoeial reference standards (RSs) certified using ISs (if available).AIM. This study aimed to certify a pharmacopoeial RS for potency testing of recombinant interferon α-2b.MATERIALS AND METHODS. The potency determination involved comparing the inhibition of the virus-induced cytopathic effect observed in cell culture with the candidate RS and the WHO International Standard for Human rDNA-derived interferon α-2b. The study used A-549 and MDBK cell lines with encephalomyocarditis (EMC) and vesicular stomatitis (VSV) viruses. The authors followed the requirements of the State Pharmacopoeia of the Russian Federation (Cell-Culture Bioassays for Interferon Products, OFS.1.7.2.0002.15). The results were recorded using instrumental and visual methods. The calculations used mathematical statistics. To factor in the influence of intermediate precision, the authors applied Student’s t-test.RESULTS. The authors developed a certification programme and procedure and certified the pharmacopoeial RS for recombinant human interferon α-2b (rhIFN α-2b) to identify the corresponding medicinal products (by virus neutralisation) and test their potency (by antiviral activity in cell culture). Upon receipt, the candidate RS was verified for compliance with regulatory specifications. According to the test results, the potency of the candidate pharmacopoeial RS was 4.47×108 IU/mL, and the expanded uncertainty was 8.12×107 IU/mL, with a coverage factor of k=2 and a confidence level of 95%. The pharmacopoeial RS for rhIFN α-2b was considered to have the same shelf-life period as the corresponding medicinal products if stored at a temperature not higher than –40 ºC. When thawed, the pharmacopoeial RS for rhIFN α-2b can be stored at a temperature of 2–8 ºC for up to 1 month.CONCLUSIONS. Upon certification for potency testing, the pharmacopoeial RS for rhIFN α-2b has been included in the Register of Reference Standards of the Russian Pharmacopoeia as Recombinant Human Interferon α-2b (Potency) FSO.3.2.00455. The introduction of this pharmacopoeial RS will help to conduct the identification and potency testing of all Russian interferon α-2b products at an appropriate scientific and methodological level. As a result, Russian pharmaceutical manufacturers and quality control agencies will no longer depend on imported ISs.

Development and validation of an analytical procedure for the determination of residual protein A in active substances of therapeutic monoclonal antibodies

SCIENTIFIC RELEVANCE. An important quality-control issue for therapeutic monoclonal antibodies (mAbs) is the determination of residual protein A leaching from the carrier during the purification of mAbs by affinity chromatography. However, unrelated compounds (immunoglobulins) present in the sample can complicate the immunoenzymatic detection of protein A (matrix effect), potentially leading to false-negative test results. To increase the efficiency of enzyme-linked immunosorbent assay (ELISA), it is necessary to develop a sample preparation step that can irreversibly break the bond in the protein A–mAb complex.AIM. This study aimed to develop and validate an analytical procedure for the determination of residual protein A in active substances of therapeutic mAbs by ELISA with a test kit comprising in-house reagents.MATERIALS AND METHODS. Recombinant protein A was used as an antigen. Polyclonal antibodies to protein A were produced by immunising chickens, selecting immunised eggs, and isolating antibodies from these eggs. Protein A-specific antibodies were purified by affinity chromatography. Residual protein A was determined using sandwich ELISA with preliminary sample preparation. The analytical procedure was validated in accordance with the requirements of the State Pharmacopoeia of the Russian Federation (Validation of Analytical Procedures, OFS.1.1.0012).RESULTS. The authors obtained, isolated, and purified chicken IgY antibodies to recombinant protein A. The authors selected sample preparation conditions for the determination of residual protein A by ELISA and optimum compositions of buffer solutions, including the composition of a denaturing buffer to disrupt the protein A–mAb complex. The developed analytical procedure was validated. According to the measurements of protein A, the accuracy of the analytical procedure ranged within 83–108% of the nominal value, the interlaboratory precision ranged within 96–116%, and the repeatability was up to 13%. The lower limit of quantitation was 10 ng/mL with a minimum required dilution of 1:10. The analytical range extended from 10 to 40 ng/mL. The analytical procedure showed results comparable to those obtained with a similar test kit from an international manufacturer.CONCLUSIONS. The developed analytical procedure for the determination of residual protein A by ELISA with a test kit comprising in-house reagents can minimise the matrix effect in therapeutic mAbs. This analytical procedure will alleviate import substitution and reduce quality control costs for Russian immunobiologicals.

Express quantitative spectrophotometric determination of 2-(((3-(2-fluorophenyl)- 5-thio-4H-1,2,4-triazol-4-yl)imino)methyl)phenol as an active substance of a medicinal product for the treatment of mycoses

Foot fungus (Candida, molds, dermatophytes) is a fairly common problem. According to the WHO, one-fifth of the world’s population is affected by fungal skin diseases. The prevalence of mycosis of the feet, which affects every second person, is especially increasing. Such a pathology can appear quite unexpectedly and at an inappropriate time. Today, Ukraine is under aggressive pressure from its northern neighbor, and military personnel are not only constantly at risk of receiving combat injuries and wounds, but also due to active hostilities, they may not have access to the necessary hygiene products, get cold, overheat in the sun, or not have time to change their clothes in time. and shoes. The reality is the absence or delay of treatment; the disease progresses and can spread quickly. If mycosis has appeared in one soldier, it can quickly affect others. Therefore, the problem of providing medical and pharmaceutical care is an urgent issue today. Expanding the assortment of drugs with the above action will ensure the needs of the Armed Forces and civilian patients with this dermatological pathology. It will be able to optimize antifungal therapy regimens. For quite a long time, 1,2,4-triazole derivatives have been a promising class of organic compounds that attract the attention of scientists from various fields. It has been proven that 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol has high antifungal activity. A potential medicinal product based on this medicinal substance can be used for the treatment of various dermatological diseases. To continue the creation of new effective dosage forms for the effective therapy of mycosis of the feet, the urgent task of today is the development of an express, accurate, reliable, and affordable method of quantitative determination of the substance under study. The aim of the work is to develop an express, sensitive and easy-to-implement UV-method for the quantitative determination of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol. Materials and methods. The research object is a working standard sample of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol provided by NUNVF, LLC “Brovapharma” according to the “Research and production technological regulations for the production of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazol-4-yl)imino)methyl)phenol” developed based on scientific developed by the Ukrainian Military Medical Academy in conjunction with the National Military Medical Clinical Center “Main Military Clinical Hospital” (term of validity of the regulations until 12/31/2034). Isopropanol of grade “chemically pure” was used as a solvent. Analytical equipment: spectrophotometer Specord 200, electronic scales Radwag XA 210.4Y, class A measuring vessels. Results. An express, eco-friendly spectrophotometric method was developed for the quantification of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol in isopropanol area, having analytically maximum at 310 nm. The studied solutions are stable for 30 minutes. The analytical technique is linear in the range of concentrations 0.440–0.754 mg/100 ml (70–130 %). The detection and quantification limits were 5.80 % and 15.70 % respectively. The score was 0.76, according to the “greenness” icon of the analytical technique, using the tools AGREE. The prediction of the total uncertainty of the results of the developed method is 1.70 % (max∆As 2.00 %). The proposed method is relevant according to the requirements of the State Pharmacopoeia of Ukraine. Conclusions. Pharmaceutical development, introduction into industrial production and further prescribing by dermatovenerologists of an effective, safe, and harmless medicinal product will help to expand the range and reduce the level of high import dependence of the domestic market of medicinal products, which will create a more complete and balanced system of medicinal supply in Ukraine and optimize antifungal therapy schemes.

Composition and technology development of ear drops with cerumenolytic action (based on thick Viscum album L. leaves extract)

Earwaxes lead to a decrease in the quality of life. A rational and effective way to eliminate earwaxes without a participation of medical personnel is to use ear drops and solutions to dissolve sulfur masses. In this regard, therapeutic and hygienic drops of а cerumenolytic action are of a particular relevance in the pharmaceutical market.The aim of the work was to develop a composition and technology of ear drops of a cerumenolytic action based on thick Viscum Album L. leaves extract.Materials and methods. The objects of the study were thick Viscum Album L. leaf extract, chitosan, sodium alginate, polyethylene oxide of various degrees of polymerization, propylene glycol, sodium hyaluronate, preservatives (benzalkonium chloride, nipagine and nipazole). At the screening stage, 9 experimental formulations were proposed. The cerumenolytic activity of the developed formulations was evaluated in a dissolution test of reproduced artificial earwax in comparison with a 3% hydrogen peroxide solution, TEA-cocoyl hydrolyzed collagen (A-Cerumen Plus, Gilbert Laboratories, France) and a 0.9% sodium chloride solution. Physical and chemical parameters (a degree of liquid coloring, turbidity and transparency, pH, density and viscosity) were determined according to of the State Pharmacopoeia of the Russian Federation (XV ed.). The microbiological study was performed using the agar diffusion method.Results. In the course of the study, it was shown that the composition of ear drops of a cerumenolytic action based on thick Viscum Album L. leaves extract, exceeds the level of a lipolytic, proteolytic and general cerumenolytic kinds of activity of the compositions containing surfactants; in its effectiveness, it was comparable with the comparison drug – A-Cerumen drops. To obtain the optimal rate of the onset effect and its duration, it is advisable to use sodium hyaluronate in the amount of 0.2 g per 25 ml of drops as an adjuvant. The most preferred preservative was benzalkonium chloride. The developed ear drops met the requirements of the State Pharmacopoeia of the Russian Federation (XV ed.) for this dosage form, while the pH was 5.86± 0.1, and the viscosity was 4.2676±0.2 MPa×s.Conclusion. The conducted research has shown the prospects for further work on the development and implementation of ear drops of a cerumenolytic action in practice. The recommended composition is the following: thick Viscum Album L. leaf extract, sodium hyaluronate, benzalkonium chloride, purified water.

EFFECT OF HUMIC FEED ADDITIVE ON METABOLIC PROCESSES AND PRODUCTIVITY OF BEEF CATTLE

The use of made in Kazakhstan organic and mineral feed additives to in-crease the meat productivity of cattle is important for the agro-industrial complex of the Republic. During the study, qualitative and quantitative analysis of raw materials was made. Quality control of the finished feed additive was carried out following the requirements of the State Pharmacopoeia of the Republic of Kazakhstan. The studies were conducted in accordance with the requirements of the Technical Regulations approved by the Decree of the Government of the Republic of Kazakhstan dated April 23, 2008 No. 380, Regulation No. 7-1/625 dated 11/28/2014 and Regulation (EC) No. 1831/2003 of the European Parliament and of the Council of September 22, 2003, on additives for use in animal feeding. Kazakh potassium humate of the Maykubensky deposit is sterile, non-pyrogenic, non-toxic, and harmless, with an average pH of 11.0-1.0, and has a biological effect on laboratory animals (white mice). The effectiveness analysis in the production experiment allowed us to identify the positive effect of feed additives on metabolic processes and increasing meat productivity in bulls. Regardless of age, on the 7th day of taking the feed additive of potassium humate, the calves' coats acquired a noticeable shine and a bright color, and shedding was completed with-in a month. Clinical signs of metabolic disorders and vitamin deficiency, detected in the farm at the time of the experiment in some animals, pass through 20-30 days from the beginning of the application of the feed additive. The optimal scheme for the use of feed additives was tested on the Kazakh meat breed Akbas, and the concentration of humic substances was selected for the maximum mani-festation of the biologically active effect. Animals became mobile and active, their rumination became more active, they grew noticeably, and the average daily weight gain increased by 7.6-8.9%.

Quality Parameters of Polyherbal Formulation of Three Different Marketed Brands of Vilwadi Gutika: A Comparative Evaluation Study

Background: Ayurveda is a highly beneficial medical system due to its natural components that effectively eliminate disease causes, restore balance, and prevent further recurrence. Polyherbal formulations are highly popular due to their wide therapeutic range, making them safe at high doses and producing minimal negative effects when taken improperly. The goal of this study was to standardize the efficacy and quality of commercial herbal tablet formulations. Methods: Three marketed samples of vilwadi Gutika ware used for the study. After authentication of the samples, the phytochemical stander like determination of pH, ash value, acid insoluble ash, water soluble ash, water soluble extractive, alcohol and soluble extractive were determined. In vitro anti-microbial activity was determined using Agar well diffusion method and the anti – inflammatory activity of Vilwadi tablet of different ayurvedic agency was assessed by in- vitro HRBC (Human Red Blood Cells) membrane stabilization method. Results: The physicochemical properties of polyherbal pills met Pharmacopeial criteria, including pH, ash value, hardness, and friability. Sample 1 was the most acceptable, with a noticeable hardness (0.93) for rapid disintegration. The sample 3 (Vilwadi gutika – Arya Vaidya Pharmacy, Coimbatore) exhibited the highest antimicrobial activity against E. coli, Staphylococcus sp, and Candida sp, while sample 1 showed the highest activity against E. coli and Staphylococcus sp, and less activity against Candida sp. The in vitro anti-inflammatory activity shown that at concentration of 100µg / ml, the test compound inhibited 66.6 % of RBC haemolysis as compared with 54.16 % produced by Indomethacin (positive control) at 100µg / ml. Conclusion: The investigation reveals that the Viladi gutika herbal formulation can be standardized using a scientific quality control technique, meeting Indian pharmacopoeia requirements for tablet dosage form, with further research needed to analyze other characteristics. Keywords: Viladi gutika, anti-microbial activity, anti-inflammatory activity.

РАЗРАБОТКА СОСТАВА, ТЕХНОЛОГИИ И ИСПЫТАНИЯ ПОЛИКОМПОНЕНТНЫХ СУППОЗИТОРИЕВ С ЭКСТРАКТОМ ПОСКОННИКА КОНОПЛЯНОГО

Hemorrhoids are one of the most common pathologies among rectal diseases, which most often affects residents of large cities around the world. This fact is explained primarily by the fact that the development of hemorrhoids is facilitated by a sedentary lifestyle of the urban population, bad habits, irregular and unbalanced nutrition, and abuse of fast-food products. The most effective way to treat hemorrhoids is surgery. However, drug therapy is no less important, both at the stage of conservative treatment and in the postoperative period. Most often, hormonal and antibacterial drugs are used to treat hemorrhoids. However, as medical practice shows, their use does not always provide a long-lasting and sustainable antihemorrhoidal effect, and is also characterized by a number of side effects associated with the possibility of systemic absorption of the active components of the drugs. In this regard, the search and development of new safe and effective drugs for the treatment and prevention of exacerbations of hemorrhoids is an urgent task of modern pharmaceutical science. When designing drugs for the treatment of hemorrhoids, it is necessary to take into account the combined clinical picture of this disease, including such manifestations as swelling, inflammation, pain, itching and burning in the rectal area. Thus, it seems appropriate to create a multifunctional antihemorrhoidal drug, which includes components of anti-inflammatory, antimicrobial and anesthetic action. It is possible to ensure such a rational combination by combining synthetic drugs and complexes of biologically active substances of plant origin One of the compositions suitable for the development of an antihemorrhoidal drug is, in our opinion, the combined presence of benzocaine and dry herb extract. Benzocaine is well known as an affordable, effective and safe local anesthetic used for local pain relief. Hemp sapling herb, in turn, is often used in folk medicine as a wound-healing, anti-inflammatory, antimicrobial, decongestant for the treatment of bruises, burns, infected wounds and ulcers of various etiologies. The most rational form for the combination of benzocaine and dry sapling herb extract proposed above seems to be suppositories. In this regard, the purpose of this study was to develop the composition, technology and testing of anti-hemorrhoidal suppositories from the sapling grass with dry extract and benzocaine. It has been established that the developed recipe for rectal suppositories on a hydrophilic basis containing polyethylene oxide 400 and 1500 is distinguished by the necessary technological properties, high bioavailability and meets the requirements of the State Pharmacopoeia of the Russian Federation XV edition.

The Effect of Cultivation Site Altitudes on the Quality Parameters of Meniran (Phylanthus niruri L.)

Meniran (Phyllanthus niruri L.) is known as a medicinal plant for immunomodulatory, hypoglycemic, diuretic treatment, and kidney disorders. It has phenolic and flavonoid as the active compounds. Several commercial products utilize meniran as the main ingredient for immunomodulators. However, the standard raw material for production has not been well reported. The study aimed to standardize the quality of meniran’s raw materials from different locations and altitudes. The phenolic compounds as the active component and their antioxidant activity were further studied. The raw materials were collected from Sukoharjo, Jember, and Karanganyar which are located from 104 masl, 243 masl, and 722 masl. The specific and non-specific standardization based on Indonesian Herbal Pharmacopoeia were investigated. The antioxidant activity was investigated. It resulted in the specific and non-specific parameters that were according to standard except for the acid soluble ash test from the Jember sample which was much higher (6.333% ± 0.969) than the standard (&lt;1.2%). In addition, the flavonoid (1.529 ± 0.167%w/w) and phenolic (1.65 ± 0.006 %w/w) content showed that the sample collected from Jember was significantly higher than other locations. However, the strongest antioxidant activity was in the sample collected from Sukoharjo (IC50 101.84μg/mL). On the other hand, there was no correlation between the total flavonoid and the total phenolic to antioxidant activity in this plant. It suggested that the antioxidant activity in these plants did not depend on the flavonoid and phenolic compounds. In conclusion, the raw material of meniran (Phyllanthus niruri L.) collected from 3 different altitudes showed the quality of herbal medicine of mainly non-specific parameters and met the requirements of Indonesian Herbal Pharmacopoeia. The total phenolic and flavonoid as the active substances varied through all 3 different altitudes. It was in line with the antioxidant activity which varied to all 3 different altitudes due to the phytochemical profile variety.

ВАЛИДАЦИЯ РЕЗУЛЬТАТОВ ИЗМЕРЕНИЙ ДЛЯ НАНОКОМПОНЕНТНЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ

Drugs containing nanoparticles are the subject of considerable interest in the field of pharmacy. They can be excellent diagnostic tools, have therapeutic properties important for the treatment of patients. Nanomaterials in the composition of drugs are widely used as carriers of poorly soluble drugs to increase both bioavailability and delivery. They enhance their therapeutic effect, reduce the harmful side effects associated with toxicity. The growing role of nanocomponent drugs leads to the fact that the quality assessment of such dosage forms should be carried out in accordance with the requirements of the state pharmacopoeia. Compliance with the requirements guarantees the quality and safety of the product. As materials and research methods were used UV spectrophotometer SF-2000, levitation melting using an induction furnace, dosage form components: active substance dioxomethyltetrahydropyrimidine, vaseline, lanolin. Quantitative determination of the components of the developed ointment with nanoparticles, carried out by UV spectrophotometry, showed that the content of the active substance dioxomethyltetrahydropyrimidine in the dosage form corresponded to the standard. The use of the validation process allows us to conclude that this ointment meets the standards and can be used for preclinical studies in order to identify the possibility of its use for the treatment of photodermatitis, ulcers, bedsores.

The Role of the Geometric Configuration of Diethylaminoethanol Derivative in the Pharmaceutical Development of a Dosage Form Based on It

Introduction. A comprehensive study of the active pharmaceutical ingredient (API) molecule is one of the defining criteria for pharmaceutical development according to the Quality by Design (QbD) concept and the ICH Q8 framework. The spatial arrangement of atoms in the molecule often has a significant impact on the physicochemical and technological properties of API, and hence on the method of producing dosage form based on it.Aim. To study some properties of substances, geometrical isomers of the molecule, which is a derivative of diethylaminoethanol (DEAE), as well as to compare the selected technologies for the preparation of dosage form.Materials and methods. The objects of the study were two substances, spatial isomers of the molecule, a derivative of DEAE, possessing neuroprotective, antiastenic and antioxidant effects. The study of properties of API and the obtained tablets was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV edition, the Pharmacopoeia of the Eurasian Economic Union, as well as the European Pharmacopoeia 9.0 edition. In this research were used substances that have not expired at the time of the study, as well as authorized for medical use.Results and discussion. The geometrical configuration of the DEAE derivative influences the properties of the API, which has an impact on the stages of pharmaceutical development, especially on the development of the technology and formulation of dosage form. The use of cis-DEAE significantly simplifies the technological process and improves the quality of the resulting drug, and as a consequence, better stability and longer shelf life of dosage form may be achieved.Conclusion. In the course of the study, some properties of cis-DEAE API were studied and compared with similar properties of trans-DEAE. A comparison of tablet preparation technologies based on the two mentioned configurations of the DEAE derivative molecule has been carried out. It was found that the isomers have different technological properties and also differ significantly in moisture adsorption capacity. This property determines the approach to tablet preparation. The technology of tablets based on cis-DEAE appears to be simpler, and dosage form based on it is more stable.

Study of the Effect of Matrix-forming Polymers on the Release Rate of Sodium 4,4'-(propanediamido)dibenzoate from Tablets

Introduction. Wet granulation technology is a process of directed particle aggregation of powder materials to obtain required properties of tablet masses and, as a consequence, to achieve satisfactory characteristics of tablets. In this addition, as a result of wet granulation technology, if special excipients are used, it becomes possible to control the rate and kinetics of release of active pharmaceutical substances from tablets to achieve the desired therapeutic effect.Aim. To study the effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of sodium 4,4'-(propanediamido)dibenzoate from tablets.Materials and methods. The original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of excipients, which included polymers used for prolonged-release dosage forms, lubricant – sodium stearyl fumarate, as well as pore-forming agents – PVP and MCC, were the objects of the study. The key parameters of tablets and dissolution kinetics were studied in accordance with the requirements of State Pharmacopoeia of the Russian Federation XIV edition and Pharmacopeia of the Eurasian Economic Union.Result and discussion. Prolonged release was achieved for all tablets, but more than 90 % of the substance was released after 12 hours in tablets containing ethylcellulose as a matrix-forming polymer. The release of APS from tablets of this formulation was the most prolonged.Сonclusion. The effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of 4,4'-(propanediamido)sodium dibenzoate from tablets has been studied. The most uniform and complete release of ASF from tablets in which the matrix-forming polymer is ethylcellulose in the amount of 27.7 %.