Pub Date : 2021-08-28DOI: 10.33380/2305-2066-2021-10-3-83-87
Yu. A. Polkovnikova
Introduction. Liposomal preparations have the following advantages: they protect body cells from the toxic effects of drugs; prolong the action of the drug introduced into the body; protect medicinal substances from degradation; promote the manifestation of targeted specificity due to selective penetration from blood into tissues; change the pharmacokinetics of drugs, increasing their pharmacological effectiveness; allow you to create a water-soluble form of a number of medicinal substances, thereby increasing their bioavailability. The development of liposomal forms of vinpocetine is highly relevant. Currently, when developing the composition of liposomal forms, molecular modeling methods are widely used, which are a convenient method for predicting both the properties of the membranes themselves and aspects of the interaction of membranes with small molecules or proteins.Aim. The aim of this study is to model the process of liposome assembly from soy lecithin phospholipids in the presence of vinpocetine by the molecular dynamics method; as well as predicting the distribution of vinpocetine between the internal cavity of the liposome, the phospholipid membrane, and the dispersion medium based on the simulation results.Materials and methods. To simulate the process of liposome formation, the method of coarse-grained molecular dynamics in a Martini 2.2 force field was used using the Gromacs 2016.4 program. The assembly of the simulated system - a solution of soy lecithin phospholipids in water was performed using the Internet service Charmm-GUI-> Inputgenerator-> Martinimaker-> Randombuilder.Results and discussion. The results of molecular modeling showed that the vinpocetine molecules did not penetrate into the liposome, but were adsorbed on its surface. This is due to the low solubility of vipocetin in the hydrophobic medium of the soy lecithin liposome membrane.Conclusion. It was shown that the minimum diameter of a liposome formed from purified soy lecithin is 15.3 nm. Vinpocetine does not penetrate into liposomes from purified soy lecithin, but is adsorbed on the outer surface of their membrane. The surface excess in this case, according to the results of modeling coarse-grained molecular dynamics at a temperature of 298 K in an alcohol-water medium, is 1.2 • 10-7 mol/m2.
{"title":"Modeling the Formation of Liposomes with Vinpocetine from Soy Lecithin Phospholipids by Molecular Dynamics","authors":"Yu. A. Polkovnikova","doi":"10.33380/2305-2066-2021-10-3-83-87","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-3-83-87","url":null,"abstract":"Introduction. Liposomal preparations have the following advantages: they protect body cells from the toxic effects of drugs; prolong the action of the drug introduced into the body; protect medicinal substances from degradation; promote the manifestation of targeted specificity due to selective penetration from blood into tissues; change the pharmacokinetics of drugs, increasing their pharmacological effectiveness; allow you to create a water-soluble form of a number of medicinal substances, thereby increasing their bioavailability. The development of liposomal forms of vinpocetine is highly relevant. Currently, when developing the composition of liposomal forms, molecular modeling methods are widely used, which are a convenient method for predicting both the properties of the membranes themselves and aspects of the interaction of membranes with small molecules or proteins.Aim. The aim of this study is to model the process of liposome assembly from soy lecithin phospholipids in the presence of vinpocetine by the molecular dynamics method; as well as predicting the distribution of vinpocetine between the internal cavity of the liposome, the phospholipid membrane, and the dispersion medium based on the simulation results.Materials and methods. To simulate the process of liposome formation, the method of coarse-grained molecular dynamics in a Martini 2.2 force field was used using the Gromacs 2016.4 program. The assembly of the simulated system - a solution of soy lecithin phospholipids in water was performed using the Internet service Charmm-GUI-> Inputgenerator-> Martinimaker-> Randombuilder.Results and discussion. The results of molecular modeling showed that the vinpocetine molecules did not penetrate into the liposome, but were adsorbed on its surface. This is due to the low solubility of vipocetin in the hydrophobic medium of the soy lecithin liposome membrane.Conclusion. It was shown that the minimum diameter of a liposome formed from purified soy lecithin is 15.3 nm. Vinpocetine does not penetrate into liposomes from purified soy lecithin, but is adsorbed on the outer surface of their membrane. The surface excess in this case, according to the results of modeling coarse-grained molecular dynamics at a temperature of 298 K in an alcohol-water medium, is 1.2 • 10-7 mol/m2.","PeriodicalId":11272,"journal":{"name":"Drug development & registration","volume":"15 12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86928100","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 : 2019-02-14DOI: 10.33380/2305-2066-2019-8-1-92-96
O. A. Lobovikova, I. V. Shul’gina, E. G. Abramova, A. K. Nikiforov, A. Komissarov, V. A. Demchenko, A. G. Selezneva, A. S. Fes'kova, S. S. Galetova, N. P. Mironova
Introduction. Documentation is an integral part of the quality management system, a key element of production and quality control of medicines. A necessary condition for the Rules of good manufacturing practice and guaranteed production of quality products is compliance with the requirements set out in the documents of the registration dossier for the drug. During the life cycle of a drug, post-registration changes in the dossier may be required. Text. This work is an analytical review of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post – registration period. The first post-registration changes in the regulatory documentation were administrative in nature and did not require examination of samples of the drug. The next group of changes in the documents of the registration dossier was due to the expansion of production, reconstruction of technological sites and the introduction of innovative technologies in order to comply with the requirements of GMP, as well as improving the consumer properties of the drug. The last group of changes concerned the revision of methods of quality control of finished products associated with the introduction of modern analytical equipment, expanding the list of standards and bringing into compliance with the requirements of the state Pharmacopoeia XIII edition. Conclusion. The timely introduction of changes into documents of the registration dossier allows you to optimize the procedure for the conduct of internal and external control of rabies immunoglobulin, as well as to avoid violations related to the actualization of the technological documentation. The analysis of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post-registration period. Timely changes in the documents of the registration dossier allow to optimize the procedure of internal and external quality control of anti-rabies immunoglobulin, as well as to avoid violations associated with the updating of technological documentation.
{"title":"REGISTRATION DOCUMENTATION AND AMENDMENTS TO IT AS AN ELEMENT OF A QUALITY MANAGEMENT SYSTEM IN PRODUCTION OF ANTI-RABIES IMMUNOGLOBULIN (REVIEW)","authors":"O. A. Lobovikova, I. V. Shul’gina, E. G. Abramova, A. K. Nikiforov, A. Komissarov, V. A. Demchenko, A. G. Selezneva, A. S. Fes'kova, S. S. Galetova, N. P. Mironova","doi":"10.33380/2305-2066-2019-8-1-92-96","DOIUrl":"https://doi.org/10.33380/2305-2066-2019-8-1-92-96","url":null,"abstract":"Introduction. Documentation is an integral part of the quality management system, a key element of production and quality control of medicines. A necessary condition for the Rules of good manufacturing practice and guaranteed production of quality products is compliance with the requirements set out in the documents of the registration dossier for the drug. During the life cycle of a drug, post-registration changes in the dossier may be required. Text. This work is an analytical review of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post – registration period. The first post-registration changes in the regulatory documentation were administrative in nature and did not require examination of samples of the drug. The next group of changes in the documents of the registration dossier was due to the expansion of production, reconstruction of technological sites and the introduction of innovative technologies in order to comply with the requirements of GMP, as well as improving the consumer properties of the drug. The last group of changes concerned the revision of methods of quality control of finished products associated with the introduction of modern analytical equipment, expanding the list of standards and bringing into compliance with the requirements of the state Pharmacopoeia XIII edition. Conclusion. The timely introduction of changes into documents of the registration dossier allows you to optimize the procedure for the conduct of internal and external control of rabies immunoglobulin, as well as to avoid violations related to the actualization of the technological documentation. The analysis of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post-registration period. Timely changes in the documents of the registration dossier allow to optimize the procedure of internal and external quality control of anti-rabies immunoglobulin, as well as to avoid violations associated with the updating of technological documentation.","PeriodicalId":11272,"journal":{"name":"Drug development & registration","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91396299","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}
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