Оценка эффективности метода двойного эмульгирования при получении микросфер налтрексона на основе сополимера молочной и гликолевой кислот

Administration of drug delivery systems allows reaching therapeutic efficiency in comparison with traditional dosage forms. Microspheres are used quite often as drug delivery systems in pharmaceutical technology. There are a polymeric carrier and a drug substance in microspheres. Incorporation of a drug substance in a polymeric matrix (carrier) extends the drug release duration by half a year. There are several methods for obtaining microspheres. Depending on the physical and chemical properties drug substances incorporate either by the double emulsification methods or by the single emulsification methods. Naltrexone hydrochloride is a water-soluble drug substance. It has antagonistic activity with respect to opioid receptors. Naltrexone incorporates into microspheres in the form of a water/oil/water type emulsion. In this work the factors that influence the size of microspheres and incorporation efficiency of Naltrexone were studied: the concentration of poly(lactic-co-glycolic acid) copolymer (PLGA); the type of the stabilizer and its concentration; the volume of an external and internal phase; the type and speed of mechanical influence on a secondary emulsion. The method of double emulsification for drug delivery systems with modified release showed low efficiency: the efficiency of Naltrexone incorporation into microspheres didn't exceed 25%.Проведена оценка эффективности метода двойного эмульгирования при получении систем с модифицированным высвобождением лекарственного вещества. Изучено влияние параметров процесса на характеристики микросфер налтрексона на основе сополимера молочной и гликолевой кислот

Исследование фармакокинетики и биодоступности в создании новых оригинальных лекарственных средств пептидной структуры и их оптимальных лекарственных форм

The review focuses on the pharmacokinetics and bioavailability studies for creating new original drugs peptide structure. Much attention is paid to methods for the quantitative determination of peptide compounds in biological material, the study of their pharmacokinetic characteristics, factors that affect the bioavailability of these substances, as well as provide some pharmacokinetic data embedded in the practice of medicines peptide structure.В обзоре акцентируется внимание на исследованиях фармакокинетики и биодоступности при создании новых оригинальных препаратов пептидной структуры. Большое внимание уделяется методам количественного определения пептидных соединений в биоматериале, изучению их фармакокинетических характеристик, факторам, влияющих на биодоступность этих веществ, а также приводятся некоторые фармакокинетические данные по внедрённым в медицинскую практику лекарственным препаратам пептидной структуры

Доклиническое изучение фармакокинетики нового анксиолитика дипетидной структуры ГБ-115

The paper presents the results of experimental studies of pharmacokinetics GB-115 after oral administration of crystalline and micronized substances and 4 new laboratory samples pharmaceutical compositions which differ in the technology of preparation and composition of excipients. It is shown that different excipients and preparation technology significantly affect the pharmacokinetics and effect of studied dipeptide; its optimization is improve the pharmacokinetics properties of the developed compound, namely increasing completeness of absorption, maximum concentration, rate and extent of absorption in the final result in bioavailability GB-115. On the basis of experimental data obtained two pharmaceutical compositions recommended for further pharmacological study.В работе представлены результаты исследования экспериментальной фармакокинетики дипептидного анксиолитика ГБ-115 после перорального введения кристаллической и микронизированной субстанций и 4-х его новых лабораторных образцов фармацевтических композиций, отличающихся по технологии приготовления и составу вспомогательных веществ. Показано, что различные вспомогательные вещества, входящие в состав фармацевтических композиций, и технология приготовления существенным образом влияют на фармакокинетику изучаемого дипептида и следствием её оптимизации является улучшение фармакокинетических свойств разрабатываемого соединения, а именно увеличения полноты всасывания, максимальной концентрации, скорости и степени всасывания и в конечном итоге биодоступности ГБ-115. На основе полученных экспериментальных данных две лекарственные композиции рекомендованы для дальнейшего фармакологического изучения

THREE-DIMENSIONAL PRINTING TECHNOLOGY FOR THE PRODUCTION OF DOSAGE FORMS

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

CREATION OF LOOPHILISATE OF GK-2 FOR PREPARATION OF SOLUTION FOR INJECTIONS WITH USE OF POLYOLS

As part of the development of the composition and technology of the lyophilized dosage form with the pharmaceutical substance (FS) GK-2, which possesses neuroprotective activity, model compositions and technological properties are studied with different temperature regimes of production. In connection with the peptide structure and low stability of the FS, the use of excipients stabilizing dosage form during the lyophilization cycle (cryoprotectants and lyoprotectors) was suggested. In this study, we selected the ratios of cryo- and lyoprotectors when using mannitol or sorbitol as a cryoprotectant, and as a lyоprotector for sucrose. Model compositions with different exipients ratios were studied by optical microscopy in polarized light to demonstrate the physical state of mannitol at different ratios of explosives. Using the Harrington generalized desirability function, the most optimal composition is chosen, which meets the requirements of SF XIII and has the most acceptable technological characteristics and optimal technological process

Estimation of efficiency of double emulsification method for the preparation of naltrexone microspheres based on poly(lactic-co-glycolic acid) copolymer

Administration of drug delivery systems allows reaching therapeutic efficiency in comparison with traditional dosage forms. Microspheres are used quite often as drug delivery systems in pharmaceutical technology. There are a polymeric carrier and a drug substance in microspheres. Incorporation of a drug substance in a polymeric matrix (carrier) extends the drug release duration by half a year. There are several methods for obtaining microspheres. Depending on the physical and chemical properties drug substances incorporate either by the double emulsification methods or by the single emulsification methods. Naltrexone hydrochloride is a water-soluble drug substance. It has antagonistic activity with respect to opioid receptors. Naltrexone incorporates into microspheres in the form of a water/oil/water type emulsion. In this work the factors that influence the size of microspheres and incorporation efficiency of Naltrexone were studied: the concentration of poly(lactic-co-glycolic acid) copolymer (PLGA); the type of the stabilizer and its concentration; the volume of an external and internal phase; the type and speed of mechanical influence on a secondary emulsion. The method of double emulsification for drug delivery systems with modified release showed low efficiency: the efficiency of Naltrexone incorporation into microspheres didn't exceed 25%