Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299165
M. Horyn, M. Piponski, O. Poliak, N. Shulyak, M. Sulyma, L. Logoyda
The aim of the work was to develop a simple, rapid, economic spectrophotometric method for the determination of meldonium in capsules based on the reaction with alizarin. Materials and methods. Analytical equipment: double-beam UV-visible spectrophotometer Shimadzu UV 1800 (Japan), a pair of 1 cm matched quartz cells, software UV-Probe 2.62, laboratory electronic balance RAD WAG AS 200/C, pH-meter И-160МИ. Pharmacopoeial standard sample (CRS) of meldonium dihydrate (Sigma-Aldrich, (≥ 98 %, HPLC)), alizarin (Synbias), capsules Metamax (Darnytsia) 250 mg, Vasopro (Farmak) 500 mg, Mildronate (Grindex) 500 mg, dimethylformamide (“Honeywell Riedel-de Haen”). Results and discussion. A spectrophotometric method for determining meldonium in capsules by reaction with alizarine has been developed. The absorption maximum of the formed complex in dimethylformamide was at a wavelength of 517 nm. Stoichiometric ratios of reactive components «meldonium- alizarin» were 1:1. Validation of the developed analytical method for the determination of meldonium in medicines was carried out in accordance with the requirements of the SPhU. The optimal conditions for performing the quantitative determination of meldonium have been established: concentration of alizarin solution – 0.8 %, volume 0.8 % alizarin solution – 0.5 ml, heating time – 20 min, temperature – 95+/- 2 °C. Linearity has been in the concentration range of 0.0402- 0.1073 mg/mL, the limit of detection - 2.84 μg/mL, and the limit of quantification – 8.59 μg/mL. The eco-friendliness of the developed analytical method was carried out using the analytical eco-scale, AGREE, and GAPI methods. Conclusions. The developed method can be used as an arbitration method for the routine analysis of meldonium capsules
{"title":"Development of the spectrophotometric method for the determination of meldonium in capsules by using alizarine","authors":"M. Horyn, M. Piponski, O. Poliak, N. Shulyak, M. Sulyma, L. Logoyda","doi":"10.15587/2519-4852.2024.299165","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299165","url":null,"abstract":"The aim of the work was to develop a simple, rapid, economic spectrophotometric method for the determination of meldonium in capsules based on the reaction with alizarin. \u0000Materials and methods. Analytical equipment: double-beam UV-visible spectrophotometer Shimadzu UV 1800 (Japan), a pair of 1 cm matched quartz cells, software UV-Probe 2.62, laboratory electronic balance RAD WAG AS 200/C, pH-meter И-160МИ. Pharmacopoeial standard sample (CRS) of meldonium dihydrate (Sigma-Aldrich, (≥ 98 %, HPLC)), alizarin (Synbias), capsules Metamax (Darnytsia) 250 mg, Vasopro (Farmak) 500 mg, Mildronate (Grindex) 500 mg, dimethylformamide (“Honeywell Riedel-de Haen”). \u0000Results and discussion. A spectrophotometric method for determining meldonium in capsules by reaction with alizarine has been developed. The absorption maximum of the formed complex in dimethylformamide was at a wavelength of 517 nm. Stoichiometric ratios of reactive components «meldonium- alizarin» were 1:1. Validation of the developed analytical method for the determination of meldonium in medicines was carried out in accordance with the requirements of the SPhU. The optimal conditions for performing the quantitative determination of meldonium have been established: concentration of alizarin solution – 0.8 %, volume 0.8 % alizarin solution – 0.5 ml, heating time – 20 min, temperature – 95+/- 2 °C. Linearity has been in the concentration range of 0.0402- 0.1073 mg/mL, the limit of detection - 2.84 μg/mL, and the limit of quantification – 8.59 μg/mL. The eco-friendliness of the developed analytical method was carried out using the analytical eco-scale, AGREE, and GAPI methods. \u0000Conclusions. The developed method can be used as an arbitration method for the routine analysis of meldonium capsules","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140415382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299229
L. Havryshchuk, V. Horishny, Nadiіa Rushchak, R. Lesyk
The aim. This review aims to provide a comprehensive understanding of dichloroacetic acid derivatives. We aim to cover all aspects of these compounds, including their chemical properties, various synthesis methods, and their wide range of applications in medicinal chemistry. By exploring their diverse roles in drug development, we aim to highlight their importance and potential in shaping future pharmaceutical innovation. Materials and methods. Bibliosemantic and analytical methods are used in the research. Results. Our studies confirm the potential effectiveness of dichloroacetic acid and its derivatives in the treatment of cancer and other diseases. These compounds can induce the apoptosis process, which is the programmed cell death, and inhibit the cancer cells' growth. This is particularly effective when dichloroacetic acid and its derivatives are used in combination with other therapeutic methods, as indicated in the patents cited in our study. Dichloroacetic acid and its derivatives have also shown the ability to lower blood glucose and cholesterol levels. This indicates the possibility of their use for diabetes, hyperlipidemia, and lactic acidosis treatment. Diabetes, hyperlipidemia, and lactic acidosis are serious conditions that can lead to significant health problems. Therefore, the possibility of using dichloroacetic acid and its derivatives for the treatment of these conditions opens new perspectives in medical science. Conclusions. Our findings point to the prospects of further research in the field of new therapy methods development and the use of dichloroacetic acid derivatives as potential drugs to improve the effectiveness of cancer and other diseases treatment. We believe that these compounds have great potential for further study and may play an important role in future medical innovation
{"title":"Dichloroacetic acid derivatives as potential anti-tumor and anti-inflammatory agents","authors":"L. Havryshchuk, V. Horishny, Nadiіa Rushchak, R. Lesyk","doi":"10.15587/2519-4852.2024.299229","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299229","url":null,"abstract":"The aim. This review aims to provide a comprehensive understanding of dichloroacetic acid derivatives. We aim to cover all aspects of these compounds, including their chemical properties, various synthesis methods, and their wide range of applications in medicinal chemistry. By exploring their diverse roles in drug development, we aim to highlight their importance and potential in shaping future pharmaceutical innovation. \u0000Materials and methods. Bibliosemantic and analytical methods are used in the research. \u0000Results. Our studies confirm the potential effectiveness of dichloroacetic acid and its derivatives in the treatment of cancer and other diseases. These compounds can induce the apoptosis process, which is the programmed cell death, and inhibit the cancer cells' growth. This is particularly effective when dichloroacetic acid and its derivatives are used in combination with other therapeutic methods, as indicated in the patents cited in our study. Dichloroacetic acid and its derivatives have also shown the ability to lower blood glucose and cholesterol levels. This indicates the possibility of their use for diabetes, hyperlipidemia, and lactic acidosis treatment. Diabetes, hyperlipidemia, and lactic acidosis are serious conditions that can lead to significant health problems. Therefore, the possibility of using dichloroacetic acid and its derivatives for the treatment of these conditions opens new perspectives in medical science. \u0000Conclusions. Our findings point to the prospects of further research in the field of new therapy methods development and the use of dichloroacetic acid derivatives as potential drugs to improve the effectiveness of cancer and other diseases treatment. We believe that these compounds have great potential for further study and may play an important role in future medical innovation","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140409924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299217
D. Leontiev, Vitalii Asmolov, N. Volovyk, Oleksandr Gryzodub
The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget. Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed. Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing. Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test
{"title":"Application of the variability budget approach to the Dissolution test","authors":"D. Leontiev, Vitalii Asmolov, N. Volovyk, Oleksandr Gryzodub","doi":"10.15587/2519-4852.2024.299217","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299217","url":null,"abstract":"The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget. \u0000Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed. \u0000Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing. \u0000Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"2018 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140416047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim. The purpose of this study is to develop the optimal composition and rational gel technology under the conventional name "Kaz-P7" based on the antifungal pomiferin. Materials and methods. The object of the study is the substance pomiferin. Based on the physicochemical properties of the gel (poorly soluble in water) and technological properties structurant - Carbopol Ultrez 20 (swelling) chosen optimal solvent system: DMSO-PG-water (1:4:1) corresponding to the maximum solubility of drug and polymer provides swelling. Following the requirements of GF RK I, vol. 1, 2.2.8, 2.2.10 was determined by rotational viscometric method. Rheological properties of the sample are determined using rotational viscometer "Rheolab QC" (firm "Anton Paar", Austria) with coaxial cylinders CC27/S-SN29766 determined. The rheological parameters were studied at a temperature of 20 °C – 35 °C using the MLM U15c thermostat included in the rheostat. Results. Gel dosage forms provide better bioavailability of the drug substance. In addition, gels are a more modern dosage form, pleasant in terms of organoleptic characteristics. The technology of gel manufacturing consists of two parallel processes: preparation of the drug substance solution and its introduction into the base. From the point of view of biopharmacy, which studies the biological effect of drugs depending on their physical properties, dosage form and preparation technology, the greatest release of the drug substance occurs when it is introduced into the dosage form in dissolved form. Pomiferin administered in the dissolved state has the most therapeutic effect on the gel base. At the same time, active pharmaceutical ingredients (APIs) were dissolved in different solvents with gradual heating. The ratio of solvents DMSO-PG-water (1:4:1) at which the developed dosage form will be more structured, stable, and thixotropic gel is established. Conclusions. Fungal skin diseases are among the most frequently discussed problems in the literature. The relevance of this topic is determined by the high prevalence of pathogens, which account for 37-42 % of all skin diseases. It was experimentally established that for the complete neutralization of one gm of carbopol Ultraz 20 in the DMSO-PG-water solvent system (1:4:1), one gm of triethanolamine (pH 7.0) is consumed. The optimal diluent consisting of DMSO-PG- water in the ratio (1:4:1) was selected by physico-chemical analysis methods, and one gm of triethanolamine (pH 7.0) was selected as the neutralizing agent. The following composition was chosen as the optimal gel model: API-3.0, DMSO-3.0, PG-50.0, Carbopol Ultrez 20-1.0, and Triethanolamine-1.0. The optimal composition and technology of the gel codenamed "Kaz-P7" based on the substance obtained by pomiferin was developed
{"title":"Development of antifungal gel, composition and technology based on pomiferin metabolite isolated from fruits of Maclura aurantiaca growing in Kazakhstan","authors":"Serzhan Mombekov, Yerkebulan Orazbekov, Nurila Sadykova, Assel Kozhamzharova, Sarzhan Sharipova, Zhaksylyk Makhatov, Nazym Pushkarskaya","doi":"10.15587/2519-4852.2024.299230","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299230","url":null,"abstract":"The aim. The purpose of this study is to develop the optimal composition and rational gel technology under the conventional name \"Kaz-P7\" based on the antifungal pomiferin. \u0000Materials and methods. The object of the study is the substance pomiferin. \u0000Based on the physicochemical properties of the gel (poorly soluble in water) and technological properties structurant - Carbopol Ultrez 20 (swelling) chosen optimal solvent system: DMSO-PG-water (1:4:1) corresponding to the maximum solubility of drug and polymer provides swelling. \u0000Following the requirements of GF RK I, vol. 1, 2.2.8, 2.2.10 was determined by rotational viscometric method. Rheological properties of the sample are determined using rotational viscometer \"Rheolab QC\" (firm \"Anton Paar\", Austria) with coaxial cylinders CC27/S-SN29766 determined. The rheological parameters were studied at a temperature of 20 °C – 35 °C using the MLM U15c thermostat included in the rheostat. \u0000Results. Gel dosage forms provide better bioavailability of the drug substance. In addition, gels are a more modern dosage form, pleasant in terms of organoleptic characteristics. \u0000The technology of gel manufacturing consists of two parallel processes: preparation of the drug substance solution and its introduction into the base. From the point of view of biopharmacy, which studies the biological effect of drugs depending on their physical properties, dosage form and preparation technology, the greatest release of the drug substance occurs when it is introduced into the dosage form in dissolved form. \u0000Pomiferin administered in the dissolved state has the most therapeutic effect on the gel base. At the same time, active pharmaceutical ingredients (APIs) were dissolved in different solvents with gradual heating. The ratio of solvents DMSO-PG-water (1:4:1) at which the developed dosage form will be more structured, stable, and thixotropic gel is established. \u0000Conclusions. Fungal skin diseases are among the most frequently discussed problems in the literature. The relevance of this topic is determined by the high prevalence of pathogens, which account for 37-42 % of all skin diseases. It was experimentally established that for the complete neutralization of one gm of carbopol Ultraz 20 in the DMSO-PG-water solvent system (1:4:1), one gm of triethanolamine (pH 7.0) is consumed. The optimal diluent consisting of DMSO-PG- water in the ratio (1:4:1) was selected by physico-chemical analysis methods, and one gm of triethanolamine (pH 7.0) was selected as the neutralizing agent. The following composition was chosen as the optimal gel model: API-3.0, DMSO-3.0, PG-50.0, Carbopol Ultrez 20-1.0, and Triethanolamine-1.0. The optimal composition and technology of the gel codenamed \"Kaz-P7\" based on the substance obtained by pomiferin was developed","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140414522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.298740
Kateryna Shchokina, S. Shtrygol', Sergii Shebeko, Halyna Bielik, T. Kutsenko, Andrii Taran
Osteoarthritis is one of the most widespread diseases, represents a medical and socio-economic problem and is one of the first places among the causes of long-term disability of the population in the world. Cytokine mechanisms of osteoarthritis development are attracting more and more attention. The aim of the study was to determine the chondroprotective and anti-inflammatory properties of the original recombinant interleukin-1 (IL-1) receptor antagonist (ARIL-1) raleukin on the model of systemic steroid osteoarthritis (SSO) in rats. Materials and methods. The SSO model was reproduced in a modified form by intramuscular three-time administration of dexamethasone at a dose of 7 mg/kg with an interval of one week. Raleukin was injected subcutaneously in a conditionally effective dose of 3 mg/kg for anti-inflammatory activity, and glucosamine (GA) orally in a dose of 50 mg/kg (ED50 for anti-inflammatory activity). Starting from the 28th day of the study and for 4 weeks, the study objects were introduced by the appropriate route once a day. Result. The results of the experiment show that clinical signs of damage to the locomotor system appeared in all animals after three administrations of dexamethasone. Later and before the end of the experiment, a typical clinical picture of the development of SSO was observed, which was confirmed by the results of the study of biochemical markers (mainly in blood serum) of the state of the connective tissue of the experimental animals. Significant changes in the functional status of the animals were noted in rats with SSO who received raleukin starting from the second week of administration. In rats, motor activity increased, tolerance to physical exertion increased, joint condition visually normalised, and appetite increased. When the reference drug GA was administered, the functional state of the animals differed from the control pathology group to a somewhat lesser extent. Besides, raleukin did not reliably differ from GA in its effect on biochemical parameters characterising the state of connective tissue and the content of its main metabolites in the blood serum of rats with steroid osteoarthritis. Conclusions. In the model of systemic steroid osteoarthritis, raleukin contributed to the improvement of functional indicators of the condition of animals and the normalisation of their body weight; namely, it moderately reduced the content of all markers of connective tissue metabolism in the blood serum of animals, especially chondroitin sulfates and sialic acids, which can be explained by the systemic nature of its effect. In terms of its effect on the level of the main metabolites of connective tissue in the blood serum of rats, raleukin prevailed over glucosamine hydrochloride. Thus, the analysis of biochemical data against the background of experimental osteoarthritis allows us to draw a conclusion about the high chondroprotective and anti-inflammatory potential of the recombinant IL-1 receptor antagonis
{"title":"Study of chondroprotective properties of interleukin-1 receptor antagonist.","authors":"Kateryna Shchokina, S. Shtrygol', Sergii Shebeko, Halyna Bielik, T. Kutsenko, Andrii Taran","doi":"10.15587/2519-4852.2024.298740","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.298740","url":null,"abstract":"Osteoarthritis is one of the most widespread diseases, represents a medical and socio-economic problem and is one of the first places among the causes of long-term disability of the population in the world. Cytokine mechanisms of osteoarthritis development are attracting more and more attention. \u0000The aim of the study was to determine the chondroprotective and anti-inflammatory properties of the original recombinant interleukin-1 (IL-1) receptor antagonist (ARIL-1) raleukin on the model of systemic steroid osteoarthritis (SSO) in rats. \u0000Materials and methods. The SSO model was reproduced in a modified form by intramuscular three-time administration of dexamethasone at a dose of 7 mg/kg with an interval of one week. Raleukin was injected subcutaneously in a conditionally effective dose of 3 mg/kg for anti-inflammatory activity, and glucosamine (GA) orally in a dose of 50 mg/kg (ED50 for anti-inflammatory activity). Starting from the 28th day of the study and for 4 weeks, the study objects were introduced by the appropriate route once a day. \u0000Result. The results of the experiment show that clinical signs of damage to the locomotor system appeared in all animals after three administrations of dexamethasone. Later and before the end of the experiment, a typical clinical picture of the development of SSO was observed, which was confirmed by the results of the study of biochemical markers (mainly in blood serum) of the state of the connective tissue of the experimental animals. \u0000Significant changes in the functional status of the animals were noted in rats with SSO who received raleukin starting from the second week of administration. In rats, motor activity increased, tolerance to physical exertion increased, joint condition visually normalised, and appetite increased. When the reference drug GA was administered, the functional state of the animals differed from the control pathology group to a somewhat lesser extent. Besides, raleukin did not reliably differ from GA in its effect on biochemical parameters characterising the state of connective tissue and the content of its main metabolites in the blood serum of rats with steroid osteoarthritis. \u0000Conclusions. In the model of systemic steroid osteoarthritis, raleukin contributed to the improvement of functional indicators of the condition of animals and the normalisation of their body weight; namely, it moderately reduced the content of all markers of connective tissue metabolism in the blood serum of animals, especially chondroitin sulfates and sialic acids, which can be explained by the systemic nature of its effect. In terms of its effect on the level of the main metabolites of connective tissue in the blood serum of rats, raleukin prevailed over glucosamine hydrochloride. Thus, the analysis of biochemical data against the background of experimental osteoarthritis allows us to draw a conclusion about the high chondroprotective and anti-inflammatory potential of the recombinant IL-1 receptor antagonis","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"672 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140417094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.291468
Tetiana Solominchuk, V. Rudiuk, Lyudmila Sidorenko, N. Kobzar, Maryna Rakhimova, Olha Vislous, V. Georgiyants
The aim: implementation of the principles of green chemistry by regenerating the synthesis solvent 1,2,4-trichlorobenzene and reusing it during the synthesis of the Naphazoline nitrate substance. Study of the influence of the regenerated solvent on the quality of the final product by controlling analytical quality parameters. Development of a method for the quantitative determination and validation of synthesis solvents in a substance. Materials and methods: samples of the substance were synthesized according to the optimized proprietary technology of Farmak JSC. The obtained batches of fresh and regenerated 1,2,4-trichlorobenzene were analyzed according to the monograph of the European Pharmacopoeia on Naphazoline nitrate 0147. Results: the possibility of using regenerated 1,2,4-trichlorobenzene for the synthesis of the substance Naphazoline nitrate has been proven. It is shown that the regenerated solvent does not have a negative effect on the profile of impurities and the polymorphic form of the substance. Analytical quality parameters met the requirements of the internal specification and the requirements of the European Pharmacopoeia monograph. The developed and validated method of quantitative determination of synthesis solvents makes it possible to determine them at the required level. Conclusions: the introduction of regenerated 1,2,4-trichlorobenzene into the synthesis scheme made it possible to significantly reduce the amount of waste per 1 kg of product, which in turn significantly reduced the negative impact on the environment. Analytical quality parameters for regenerated 1,2,4-trichlorobenzene meet the requirements of the internal specification. Industrial series obtained on the regenerated solvent meet the requirements of the monograph of the European Pharmacopoeia. The polymorphic form of the substance batches manufactured on regenerated 1,2,4-trichlorobenzene corresponds to the polymorphic form of the substance batches manufactured on the fresh solvent. The obtained results on the influence of the regenerated solvent on the profile of impurities in the finished substance show the similarity of the profile of the series manufactured on both solvents. According to the requirements of ICH Q3C Impurities: Guideline for residual solvents, a method for quantitative determination of the residual content of 1,2,4-trichlorobenzene in the final product by gas chromatography was developed and validated. The absence of synthesis solvents at the limit of detection is shown
目的：通过再生合成溶剂 1,2,4-三氯苯并在硝酸萘甲唑啉物质的合成过程中重复使用该溶剂，落实绿色化学原则。通过控制分析质量参数，研究再生溶剂对最终产品质量的影响。材料和方法：根据 Farmak 股份公司优化的专利技术合成物质样品。根据《欧洲药典》关于硝酸萘甲唑啉的专著 0147，对获得的新鲜和再生 1,2,4-三氯苯批次进行了分析。结果：使用再生 1,2,4-三氯苯合成硝酸萘甲唑啉的可能性已经得到证实。结果表明，再生溶剂不会对杂质和物质的多晶型产生负面影响。分析质量参数符合内部规范和欧洲药典专著的要求。结论：在合成方案中引入再生的 1,2,4-三氯苯可显著减少每公斤产品的废物量，从而大大减少对环境的负面影响。再生 1,2,4-三氯苯的分析质量参数符合内部规范要求。再生溶剂的工业系列符合《欧洲药典》专论的要求。用再生的 1,2,4-三氯苯生产的物质批次的多形态形式与用新鲜溶剂生产的物质批次的多形态形式一致。再生溶剂对成品物质中杂质分布的影响结果表明，用这两种溶剂生产的系列物质的杂质分布具有相似性。根据 ICH Q3C 杂质：根据 ICH Q3C《杂质：残留溶剂指南》的要求，开发并验证了利用气相色谱法定量测定成品中 1,2,4-三氯苯残留量的方法。结果表明，在检测限内不存在合成溶剂。
{"title":"Solvents in the industrial synthesis of naphazoline nitrate: implementation of the principles of \"Green chemistry\" and analysis","authors":"Tetiana Solominchuk, V. Rudiuk, Lyudmila Sidorenko, N. Kobzar, Maryna Rakhimova, Olha Vislous, V. Georgiyants","doi":"10.15587/2519-4852.2024.291468","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.291468","url":null,"abstract":"The aim: implementation of the principles of green chemistry by regenerating the synthesis solvent 1,2,4-trichlorobenzene and reusing it during the synthesis of the Naphazoline nitrate substance. Study of the influence of the regenerated solvent on the quality of the final product by controlling analytical quality parameters. Development of a method for the quantitative determination and validation of synthesis solvents in a substance.\u0000Materials and methods: samples of the substance were synthesized according to the optimized proprietary technology of Farmak JSC. The obtained batches of fresh and regenerated 1,2,4-trichlorobenzene were analyzed according to the monograph of the European Pharmacopoeia on Naphazoline nitrate 0147.\u0000Results: the possibility of using regenerated 1,2,4-trichlorobenzene for the synthesis of the substance Naphazoline nitrate has been proven. It is shown that the regenerated solvent does not have a negative effect on the profile of impurities and the polymorphic form of the substance. Analytical quality parameters met the requirements of the internal specification and the requirements of the European Pharmacopoeia monograph. The developed and validated method of quantitative determination of synthesis solvents makes it possible to determine them at the required level.\u0000Conclusions: the introduction of regenerated 1,2,4-trichlorobenzene into the synthesis scheme made it possible to significantly reduce the amount of waste per 1 kg of product, which in turn significantly reduced the negative impact on the environment. Analytical quality parameters for regenerated 1,2,4-trichlorobenzene meet the requirements of the internal specification. Industrial series obtained on the regenerated solvent meet the requirements of the monograph of the European Pharmacopoeia. The polymorphic form of the substance batches manufactured on regenerated 1,2,4-trichlorobenzene corresponds to the polymorphic form of the substance batches manufactured on the fresh solvent. The obtained results on the influence of the regenerated solvent on the profile of impurities in the finished substance show the similarity of the profile of the series manufactured on both solvents. According to the requirements of ICH Q3C Impurities: Guideline for residual solvents, a method for quantitative determination of the residual content of 1,2,4-trichlorobenzene in the final product by gas chromatography was developed and validated. The absence of synthesis solvents at the limit of detection is shown","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140408344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299266
R. Khaleel, S. M. Shareef, Tayf Mohammed Maryoosh
Psoriasis is an underestimated chronic and autoimmune skin disorder. Topical chemical agents are applied for psoriasis control and treatment, notwithstanding their subordinate efficiency or unsuccessful activities. As an alternative, herbal medicine can also be used in its treatment. The aim of the present study was performed to assess the anti-psoriasis effect of Scrophularia deserti in mice model. Materials and methods: S. deserti was purchased and used for methanolic extraction. Extract DPPH radical scavenging activity, polyphenol and flavonoid contents were examined. Sixty male mice were purchased, and psoriasis was induced using 10 days of topical administration of Imiquimod (62.5 mg). Mice were classified into 6 groups: non-psoriasis control (only received distilled water), psoriasis control (only received topical Imiquimod), two S. deserti treatments (topical 300 and 500 mg/kg), topical Betamethasone, and topical α-pinene 9 %. Cytokine distribution and histopathological properties were also determined. Results: the value at which the S. deserti methanolic extract scavenges 50 % of free radicals (IC50) was 602.71±15.33 µg/mL. The total S. deserti methanolic extract flavonoid and polyphenol contents were 16.85±1.12 mg QE/g and 58.47±3.25 mg GAE/g, respectively. IL-22, TNF-α, and IL-17A concentrations increased after psoriasis induction compared to the control group (P <0.05). Mice treated with Betamethasone harboured the lowest concentrations of IL-22, TNF-α, and IL-17A (P <0.05). Conclusions: Mice treated with S. deserti methanolic extract (500 mg/kg) also harboured significantly lower IL-22, TNF-α, and IL-17A (P <0.05) compared to α-pinene and S. deserti methanolic extract (300 mg/kg). Mice of the psoriasis control group showed significant epidermis hyperkeratosis, acanthosis, and crust with plentiful inflammatory cells. At the same time, mice treated with S. deserti methanolic extract (500 mg/kg) showed significant recovered tissue with normal skin epidermis and dermis, sebaceous glands, and follicles of the hair, besides the lowest rate of inflammatory reactions. Findings showed that the S. deserti methanolic extract (500 mg/kg) can efficiently be used as a practical substitute for psoriasis treatment. However, some supplementary research should be performed
{"title":"Assessment of the anti-psoriasis effect of Scrophularia deserti methanolic extract in mice model","authors":"R. Khaleel, S. M. Shareef, Tayf Mohammed Maryoosh","doi":"10.15587/2519-4852.2024.299266","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299266","url":null,"abstract":"Psoriasis is an underestimated chronic and autoimmune skin disorder. Topical chemical agents are applied for psoriasis control and treatment, notwithstanding their subordinate efficiency or unsuccessful activities. As an alternative, herbal medicine can also be used in its treatment. \u0000The aim of the present study was performed to assess the anti-psoriasis effect of Scrophularia deserti in mice model. \u0000Materials and methods: S. deserti was purchased and used for methanolic extraction. Extract DPPH radical scavenging activity, polyphenol and flavonoid contents were examined. Sixty male mice were purchased, and psoriasis was induced using 10 days of topical administration of Imiquimod (62.5 mg). Mice were classified into 6 groups: non-psoriasis control (only received distilled water), psoriasis control (only received topical Imiquimod), two S. deserti treatments (topical 300 and 500 mg/kg), topical Betamethasone, and topical α-pinene 9 %. Cytokine distribution and histopathological properties were also determined. \u0000Results: the value at which the S. deserti methanolic extract scavenges 50 % of free radicals (IC50) was 602.71±15.33 µg/mL. The total S. deserti methanolic extract flavonoid and polyphenol contents were 16.85±1.12 mg QE/g and 58.47±3.25 mg GAE/g, respectively. IL-22, TNF-α, and IL-17A concentrations increased after psoriasis induction compared to the control group (P <0.05). Mice treated with Betamethasone harboured the lowest concentrations of IL-22, TNF-α, and IL-17A (P <0.05). \u0000Conclusions: Mice treated with S. deserti methanolic extract (500 mg/kg) also harboured significantly lower IL-22, TNF-α, and IL-17A (P <0.05) compared to α-pinene and S. deserti methanolic extract (300 mg/kg). Mice of the psoriasis control group showed significant epidermis hyperkeratosis, acanthosis, and crust with plentiful inflammatory cells. At the same time, mice treated with S. deserti methanolic extract (500 mg/kg) showed significant recovered tissue with normal skin epidermis and dermis, sebaceous glands, and follicles of the hair, besides the lowest rate of inflammatory reactions. Findings showed that the S. deserti methanolic extract (500 mg/kg) can efficiently be used as a practical substitute for psoriasis treatment. However, some supplementary research should be performed","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"21 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140411330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299177
I. Sych, Olena Bevz, I. Sych, Nayak Sanjay Kumar, O. Kryvanych, Olha Vislous, V. Yaremenko, Maryna Rakhimova, L. Perekhoda
Synthetic cannabinoids are a group of psychoactive compounds that mimic the effects of Δ9-tetrahydrocannabinol, the main psychoactive component of marijuana. Today, the most important task in forensic science is to establish the chemical structure of new psychoactive compounds that appear in illicit trafficking promptly in order to respond quickly and stop their distribution. Less important is the development of methodological support for expert activity, including analysis methods and reference data on the analytical characteristics of compounds. The aim. To develop stages of the forensic analysis of objects containing synthetic cannabinoids and propose methods for determining 5 new synthetic cannabinoids for forensic pharmaceutical purposes. Materials and methods. The study was conducted as part of the identification of cannabinoids for forensic purposes at the National Scientific Centre "Bokarius Institute of Forensic Examination". As part of the study, 5 new synthetic cannabinoids were identified for forensic analysis using the following methods: infrared spectroscopy, thin-layer chromatography, and gas chromatography with a mass detector. The algorithm for the forensic analysis of cannabinoid derivatives was developed based on the requirements of Ukraine's current legislation. Results. Spectral and chromatographic methods of determination of 5 new synthetic cannabinoids for forensic purposes were proposed, and during research and elaboration of the current legislation of Ukraine, an algorithm for forensic investigation of objects containing synthetic cannabinoids has been developed. Conclusions. The stages of the forensic analysis of objects containing synthetic cannabinoids meet the requirements of the current legislation of Ukraine and the Ministry of Justice of Ukraine. The obtained data prove the high sensitivity and reproducibility of the methods and prove the possibility of their introduction into the practice of forensic examination
{"title":"Chemical and pharmaceutical research of cannabinoids as objects of forensic examination","authors":"I. Sych, Olena Bevz, I. Sych, Nayak Sanjay Kumar, O. Kryvanych, Olha Vislous, V. Yaremenko, Maryna Rakhimova, L. Perekhoda","doi":"10.15587/2519-4852.2024.299177","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299177","url":null,"abstract":"Synthetic cannabinoids are a group of psychoactive compounds that mimic the effects of Δ9-tetrahydrocannabinol, the main psychoactive component of marijuana. Today, the most important task in forensic science is to establish the chemical structure of new psychoactive compounds that appear in illicit trafficking promptly in order to respond quickly and stop their distribution. Less important is the development of methodological support for expert activity, including analysis methods and reference data on the analytical characteristics of compounds. \u0000The aim. To develop stages of the forensic analysis of objects containing synthetic cannabinoids and propose methods for determining 5 new synthetic cannabinoids for forensic pharmaceutical purposes. \u0000Materials and methods. The study was conducted as part of the identification of cannabinoids for forensic purposes at the National Scientific Centre \"Bokarius Institute of Forensic Examination\". As part of the study, 5 new synthetic cannabinoids were identified for forensic analysis using the following methods: infrared spectroscopy, thin-layer chromatography, and gas chromatography with a mass detector. The algorithm for the forensic analysis of cannabinoid derivatives was developed based on the requirements of Ukraine's current legislation. \u0000Results. Spectral and chromatographic methods of determination of 5 new synthetic cannabinoids for forensic purposes were proposed, and during research and elaboration of the current legislation of Ukraine, an algorithm for forensic investigation of objects containing synthetic cannabinoids has been developed. \u0000Conclusions. The stages of the forensic analysis of objects containing synthetic cannabinoids meet the requirements of the current legislation of Ukraine and the Ministry of Justice of Ukraine. The obtained data prove the high sensitivity and reproducibility of the methods and prove the possibility of their introduction into the practice of forensic examination","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"29 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140414063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299184
Valeriia Cherniakova, A. Myhal, V. Rudiuk, O. Kryvanych, O. Rudakova, Igor Tugaibei, N. Bevz, V. Georgiyants
The aim of the work is the development of chromatographic conditions, the study of the validation characteristics of the method of quantitative determination of phenylephrine hydrochloride, nitrofural, lidocaine hydrochloride and diphenhydramine hydrochloride, panthenol, povidone in the joint presence in the nasal spray by a complex method of liquid chromatography with UV detection. Evaluation of the quantitative content of active components after manufacturing and during the shelf life. Materials and methods. Agilent 1260 liquid chromatographs, equipped with a diode-matrix detector from the company "Agilent technologies", USA. Chromatographic columns 250×4.6 mm in size, filled with octadecylsilyl silica gel for chromatography (Zorbax StableBond SB-Aq, Agilent company), mobile phase A - phosphate buffer solution pH 7.0 - acetonitrile P (1650:350), mobile phase B – acetonitrile P; elution mode – gradient; mobile phase flow rate – 1.0 ml/min; detection wavelengths – 220 nm (for panthenol, phenylephrine, povidone, diphenhydramine) and 235 nm (for nitrofural and lidocaine). Results. Chromatographic separation conditions were developed for the co-presence determination of six target substances: panthenol, phenylephrine hydrochloride, nitrofural, povidone, lidocaine hydrochloride and diphenhydramine hydrochloride. The suitability of the technique for this task was confirmed by determining the validation characteristics. The methodology at the appropriate level is characterized by specificity, linearity, correctness and convergence in the range of application for panthenol (range 20.33-38.26 mg/ml, ΔZ=0.93 ≤ max ΔZ=3.20, a=0.63 max a=5.12, r = 0.9978 min r= 0.9924), phenylephrine hydrochloride (range 1,70-3,21 mg/ml, ΔZ=0.51 ≤ max ΔZ=3.20, a=0.15 max a=5.12, r = 0.9984 min r= 0.9924), nitrofural (range 0.137-0.257 mg/ml, ΔZ=0.91 ≤ max ΔZ=3.20, a=0.032 max a=5.12, r = 0.9987 min r= 0.9924) povidone (range 20,44-38,50 mg/ml, ΔZ=0.23 ≤ max ΔZ=3.20, a=2,33 max a=5.12, r = 0.9942 min r= 0.9924), lidocaine hydrochloride (range 6,80-12,81 mg/ml, ΔZ=0.34 ≤ max ΔZ=3.20, a=0.66 max a=5.12, r = 0.9988 min r= 0.9924), diphenhydramine hydrochloride (range 1,36-2,56 mg/ml, ΔZ=0.20 ≤ max ΔZ=3.20, a=0.15 max a=5.12, r = 0.9980 min r= 0.9924). There are no significant changes when stored at 25 °C for 6 months. Conclusions. An analytical method of quantitative determination of the component composition in an extemporaneous nasal spray by a complex method of high-performance liquid chromatography has been developed. The determined validation parameters confirm the correctness of the methodology. The chemical stability of the dosage form is observed for 6 months
这项工作的目的是开发色谱条件，研究采用复合液相色谱法和紫外检测法定量测定鼻腔喷雾剂中盐酸去氧肾上腺素、硝基呋喃、盐酸利多卡因和盐酸苯海拉明、泛醇、聚维酮的方法的验证特性。评估生产后和保质期内活性成分的定量含量。材料和方法美国 "安捷伦科技 "公司生产的安捷伦 1260 型液相色谱仪，配有二极管矩阵检测器。色谱柱尺寸为 250×4.6 毫米，填充有十八烷基硅烷色谱硅胶（Zorbax StableBond SB-Aq，安捷伦公司），流动相 A - 磷酸盐缓冲溶液 pH 7.0 - 乙腈 P（1650:350），流动相 B - 乙腈 P；洗脱模式 - 梯度；流动相流速 - 1.0 ml/min；检测波长 - 220 nm（泛醇、苯肾上腺素、聚维酮、苯海拉明）和 235 nm（硝基糠醛和利多卡因）。结果为同时测定六种目标物质：泛醇、盐酸去氧肾上腺素、硝基呋喃、聚维酮、盐酸利多卡因和盐酸苯海拉明制定了色谱分离条件。通过确定验证特征，确认了该技术对这项任务的适用性。在泛醇的应用范围内，适当水平的方法具有特异性、线性、正确性和收敛性（范围 20.33-38.26 mg/ml，ΔZ=0.93 ≤最大 ΔZ=3.20，a=0.63 max a=5.12, r = 0.9978 min r= 0.9924）、盐酸肾上腺素（范围 1,70-3,21 mg/ml，ΔZ=0.51 ≤ max ΔZ=3.20，a=0.15 max a=5.12，r = 0.9984 min r=0.9924）、硝基糠醛（范围 0.137-0.257 mg/ml，ΔZ=0.91 ≤ max ΔZ=3.20, a=0.032 max a=5.12, r = 0.9987 min r= 0.9924）聚维酮（范围 20,44-38,50 mg/ml，ΔZ=0.23 ≤ max ΔZ=3.20, a=2,33 max a=5.12, r = 0.9942 min r= 0.9924）、盐酸利多卡因（范围 6,80-12,81 mg/ml，ΔZ=0.34 ≤ max ΔZ=3.20，a=0.66 max a=5.12，r=0.9988 min r=0.9924）、盐酸苯海拉明（范围 1.36-2.56 mg/ml，ΔZ=0.20 ≤ max ΔZ=3.20，a=0.15 max a=5.12，r=0.9980 min r=0.9924）。在 25 °C 下存放 6 个月后，没有明显变化。结论通过高效液相色谱复合方法，开发了一种定量测定即用鼻腔喷雾剂成分的分析方法。确定的验证参数证实了该方法的正确性。该剂型的化学稳定性可观察 6 个月。
{"title":"Determination of chromatographic conditions for quantitative assessment of active components in complex nasal spray after manufacturing and expiry date","authors":"Valeriia Cherniakova, A. Myhal, V. Rudiuk, O. Kryvanych, O. Rudakova, Igor Tugaibei, N. Bevz, V. Georgiyants","doi":"10.15587/2519-4852.2024.299184","DOIUrl":"https://doi.org/10.15587/2519-4852.2024.299184","url":null,"abstract":"The aim of the work is the development of chromatographic conditions, the study of the validation characteristics of the method of quantitative determination of phenylephrine hydrochloride, nitrofural, lidocaine hydrochloride and diphenhydramine hydrochloride, panthenol, povidone in the joint presence in the nasal spray by a complex method of liquid chromatography with UV detection. Evaluation of the quantitative content of active components after manufacturing and during the shelf life. \u0000Materials and methods. Agilent 1260 liquid chromatographs, equipped with a diode-matrix detector from the company \"Agilent technologies\", USA. Chromatographic columns 250×4.6 mm in size, filled with octadecylsilyl silica gel for chromatography (Zorbax StableBond SB-Aq, Agilent company), mobile phase A - phosphate buffer solution pH 7.0 - acetonitrile P (1650:350), mobile phase B – acetonitrile P; elution mode – gradient; mobile phase flow rate – 1.0 ml/min; detection wavelengths – 220 nm (for panthenol, phenylephrine, povidone, diphenhydramine) and 235 nm (for nitrofural and lidocaine). \u0000Results. Chromatographic separation conditions were developed for the co-presence determination of six target substances: panthenol, phenylephrine hydrochloride, nitrofural, povidone, lidocaine hydrochloride and diphenhydramine hydrochloride. The suitability of the technique for this task was confirmed by determining the validation characteristics. The methodology at the appropriate level is characterized by specificity, linearity, correctness and convergence in the range of application for panthenol (range 20.33-38.26 mg/ml, ΔZ=0.93 ≤ max ΔZ=3.20, a=0.63 max a=5.12, r = 0.9978 min r= 0.9924), phenylephrine hydrochloride (range 1,70-3,21 mg/ml, ΔZ=0.51 ≤ max ΔZ=3.20, a=0.15 max a=5.12, r = 0.9984 min r= 0.9924), nitrofural (range 0.137-0.257 mg/ml, ΔZ=0.91 ≤ max ΔZ=3.20, a=0.032 max a=5.12, r = 0.9987 min r= 0.9924) povidone (range 20,44-38,50 mg/ml, ΔZ=0.23 ≤ max ΔZ=3.20, a=2,33 max a=5.12, r = 0.9942 min r= 0.9924), lidocaine hydrochloride (range 6,80-12,81 mg/ml, ΔZ=0.34 ≤ max ΔZ=3.20, a=0.66 max a=5.12, r = 0.9988 min r= 0.9924), diphenhydramine hydrochloride (range 1,36-2,56 mg/ml, ΔZ=0.20 ≤ max ΔZ=3.20, a=0.15 max a=5.12, r = 0.9980 min r= 0.9924). There are no significant changes when stored at 25 °C for 6 months. \u0000Conclusions. An analytical method of quantitative determination of the component composition in an extemporaneous nasal spray by a complex method of high-performance liquid chromatography has been developed. The determined validation parameters confirm the correctness of the methodology. The chemical stability of the dosage form is observed for 6 months","PeriodicalId":21674,"journal":{"name":"ScienceRise: Pharmaceutical Science","volume":"2003 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140416496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.15587/2519-4852.2024.299205
I. Botsula, Igor Kireyev, O. Koshovyi, J. Heinämäki, R. Ain, Maryna Mazur, V. Chebanov
Anxiety disorders are the most prevalent psychiatric disorders and are associated with a high burden of illness. Combining synthetic and native-origin compounds in treating such disorders could provide true benefits in terms of therapeutic efficacy. In the present study, we combined triazolobenzodiazepine and motherwort (Leonurus cardiaca L.) dry extract for such applications. The aim. The aim of this study was to develop aqueous polyethylene oxide (PEO) composite gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort herb dry extract for semi-solid extrusion (SSE) 3D printing. The printability of such gels and the physicochemical properties of the final 3D-printed drug preparations were investigated. Materials and methods. A new drug substance, 1,2,3-triazolo-1,4-benzodiazepine (MA-253) was synthesized and used to formulate oleogels and electrospun nanofibers for 3D printing. The plant-origin dry extract was prepared from a motherwort tincture and valine. The aqueous PEO gels loaded with a synthetic drug (MA-253) containing nanofibers and a valine-modified motherwort extract were prepared and subsequently used in the SSE 3D printing experiments. The homogeneity, viscosity and 3D printability of composite PEO gels were verified. The phytochemical assay of flavonoids in the 3D-printed drug preparations was conducted with the European pharmacopoeia spectrophotometric method. Research results. Three experimental gel formulations loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort dry extract were developed and tested for the SSE 3D printing applications. The present three gels showed good SSE 3D printability without any significant printing flaws. The SSE 3D-printed lattices prepared from the aqueous PEO gels containing 100 mg/ml of motherwort extract showed the most promising 3D printing performance. The 3D-printed drug preparations were entirely dissolved in purified water (22±2 °C) within 20 minutes, thus suggesting their applicability in oral administration. Conclusions. Novel aqueous PEO gel formulations loaded with nanofibrous 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort herb extract are feasible for pharmaceutical SSE 3D printing. The present composite PEO gels enable the preparation of printed oral immediate-release drug delivery systems for new triazolobenzodiazepine derivatives and a drug therapy supportive plant extract
焦虑症是最常见的精神疾病，也是一种高负担疾病。在治疗此类疾病时，将合成化合物和本地原产化合物结合使用，可在疗效方面带来真正的益处。在本研究中，我们将三唑类苯并二氮杂卓与益母草（Leonurus cardiaca L.）干提取物相结合，用于此类应用。研究目的本研究的目的是开发一种水性聚氧化乙烯（PEO）复合凝胶，其中装有 1,2,3 三唑并-1,4-苯并二氮杂卓纳米纤维和一种缬氨酸改性益母草干提取物，用于半固态挤出（SSE）三维打印。研究了这种凝胶的可打印性以及最终 3D 打印药物制剂的理化性质。材料和方法合成了一种新的药物物质--1,2,3-三唑并-1,4-苯并二氮杂卓（MA-253），并将其用于配制油凝胶和电纺纳米纤维以进行三维打印。植物源干提取物由益母草酊和缬氨酸制备而成。制备了负载合成药物（MA-253）的水性 PEO 凝胶，其中含有纳米纤维和缬氨酸改性的益母草提取物，随后将其用于 SSE 3D 打印实验。实验验证了复合 PEO 凝胶的均匀性、粘度和 3D 打印性能。采用欧洲药典分光光度法对 3D 打印药物制剂中的黄酮类化合物进行了植物化学分析。研究结果开发并测试了三种负载 1,2,3-三唑并-1,4-苯并二氮杂卓纳米纤维和缬氨酸改性益母草干提取物的实验性凝胶配方，并将其应用于 SSE 3D 打印。这三种凝胶显示出良好的 SSE 3D 打印性能，没有任何明显的打印缺陷。由含有 100 毫克/毫升益母草提取物的水性 PEO 凝胶制备的 SSE 3D 打印晶格显示出最有前途的 3D 打印性能。3D 打印的药物制剂在 20 分钟内完全溶解在纯净水（22±2 °C）中，这表明它们适用于口服给药。结论新型水性 PEO 凝胶制剂负载有 1,2,3- 三唑并-1,4-苯并二氮杂卓纳米纤维和缬氨酸改性益母草提取物，可用于药物 SSE 3D 打印。目前的复合 PEO 凝胶可用于制备新型三唑并二氮卓衍生物和一种药物治疗辅助植物提取物的打印口服速释给药系统。
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