pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2019-7-3-138-147pmedpharm-397Research ArticleФАРМАЦЕВТИЧЕСКАЯ И ТОКСИКОЛОГИЧЕСКАЯ ХИМИЯPHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRYОПТИМИЗАЦИЯ СПОСОБА ПОЛУЧЕНИЯ НАНОКАПСУЛ, РАЗРАБОТКА МЕТОДИКИ ОПРЕДЕЛЕНИЯ СТЕПЕНИ ВКЛЮЧЕНИЯ ЦИННАРИЗИНА В ПРОЛОНГИРОВАННУЮ ЛЕКАРСТВЕННУЮ ФОРМУНА ОСНОВЕ ПОЛИ-D,L-ЛАКТИД-КО-ГЛИКОЛИДА И ЕЕ ВАЛИДАЦИЯOPTIMIZATION OF THE METHOD FOR OBTAINING NANOCAPSULES, DEVELOPMENT OF THE METHODS OF DETERMINING THE DEGREE OF CINNARIZINE INCLUSION IN A PROLONGED DOSAGE FORM BASED ON POLY-D, L-LACTID-CO-GLICOLIDE, AND ITS VALIDATIONhttps://orcid.org/0000-0003-0590-8256СорокоумоваМ. В.SorokoumovaM. V.

аспирант кафедры неорганической, физической и коллоидной химии, 

357532, Ставропольский край, г. Пятигорск, пр. Калинина, 11

Postgraduate student of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

mariya_026@mail.ruhttps://orcid.org/0000-0002-9302-097XБлагоразумнаяН. В.BlagorazumnayaN. V.

кандидат фармацевтических наук, доцент кафедры фармацевтической химии и токсикологии,

 

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Pharmaceutical and Toxicological Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

nataliyva@rambler.ruhttps://orcid.org/0000-0001-9560-5288КомпанцевВ. А.KompantsevV. A.

доктор фармацевтических наук, профессор кафедры неорганической, физической и коллоидной химии,

 

Doctor of Pharmaceutical Sciences, Professor of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

l.i.sherbakova@pmedpharm.ruhttps://orcid.org/0000-0002-7806-2805ЩербаковаЛ. И.ShcherbakovaL. I.

кандидат фармацевтических наук, доцент,зав. кафедрой,

 

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

l.i.sherbakova@pmedpharm.ruhttps://orcid.org/0000-0001-6007-1204ЗяблицеваН. С.ZyablitsevaN. S.

кандидат фармацевтических наук, доцент преподаватель кафедры неорганической, физической и коллоидной химии,

 

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

n.s.zyablitseva@yandex.ruМедвецкаяЮ. Г.MedvetskayaYu. G.

кандидат фармацевтических наук, старший преподаватель кафедры неорганической, физической и коллоидной химии,

 

Candidate of Pharmaceutical Sciences, Senior Lecturer of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

https://orcid.org/0000-0001-6816-3883ВасинаТ. М.VasinaT. M.

кандидат фармацевтических наук, доцент преподаватель кафедры неорганической, физической и коллоидной химии,

 

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Inorganic, Physical and Colloid Chemistry,

11, Kalinin ave., Pyatigorsk, 357532

tatyana.vasina.5959@mail.ruhttps://orcid.org/0000-0002-9811-1678МирошниченкоК. А.MiroshnichenkoK. A.

студент 5 курса,

 

5-year student,

11, Kalinin ave., Pyatigorsk, 357532

k220436@yandex.ruПятигорский медико-фармацевтический институт – филиал ФГБОУ ВО Волгоградский государственный медицинский университет Минздрава РоссииРоссияPyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical UniversityRussian Federation20190907201973138147Copyright © Сорокоумова М.В., Благоразумная Н.В., Компанцев В.А., Щербакова Л.И., Зяблицева Н.С., Медвецкая Ю.Г., Васина Т.М., Мирошниченко К.А., 20192019Сорокоумова М.В., Благоразумная Н.В., Компанцев В.А., Щербакова Л.И., Зяблицева Н.С., Медвецкая Ю.Г., Васина Т.М., Мирошниченко К.А.Sorokoumova M.V., Blagorazumnaya N.V., Kompantsev V.A., Shcherbakova L.I., Zyablitseva N.S., Medvetskaya Y.G., Vasina T.M., Miroshnichenko K.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/397

Распространенными патологиями сердечно-сосудистой системы являются цереброваскулярные расстройства, для лечения которых назначают препарат циннаризин. Разработана инновационная пролонгированная лекарственная форма в виде нанокапсул на основе поли-D,L-лактид-ко-гликолид (PLGA).

Целью исследования явилось совершенствование технологии и разработка методики определения уровня включения циннаризина в нанокапсулы. Исследовательская проблема заключалась в наличии множества особенностей инкапсулирования препарата, а также различных физико-химических свойств веществ, которые невозможно учесть в имеющихся методиках определения.

Материалы и методы

Материалы и методы. В ходе исследования были использованы субстанция циннаризина, PLGA (50:50), поливиниловый спирт (ПВС). Остальные реактивы и растворители соответствовали категории х.ч. Для разработки методики количественного определения циннаризина и ее валидации, использован спектрофотометрический метод анализа. Были приготовлены модельные смеси, которые использовались как объекты исследования. Валидационную оценку методики проводили по таким показателям, как специфичность, линейность, предел обнаружения, повторяемость, воспроизводимость.

Результаты

Результаты. Разработана методика спектрофотометрического определения степени включения циннаризина. Установлено, что инкапсуляция составляет 63,74%. Осуществлено валидационное тестирование методики. Результаты таких испытаний, как специфичность, линейность, предел обнаружения, повторяемость, воспроизводимость соответствуют допустимому интервалу значений, регламентированных нормативной документацией. Скорректирована технология получения нанокапсул, в связи с невозможностью определения степени включения циннаризина при использовании стандартной методики получения.

Заключение

Заключение. Оптимизирована технология и разработана методика, позволяющая провести достоверный анализ степени включения циннаризина в нанокапсулы, с учетом особенностей производства и физико-химических свойств компонентов. Относительная погрешность разработанной методики определения не превышает ±2,67%. Исходя из результатов валидационой оценки, по всем показателям методика валидна. 

Common pathologies of the cardiovascular system are cerebrovascular disorders, for which cinnarizine is prescribed. An innovative, prolonged nanocapsule dosage form based on poly-D, L-lactide-co-glycolide (PLGA) has been developed.

The aim of the research was improvement of the technology and development of the methods for determining the level of cinnarizine inclusion in nanocapsules. The research problem consisted of a great number of drug encapsulation peculiarities, as well as various physicochemical properties of the substances that cannot be taken into account in the existing methods of determination.

Materials and methods

Materials and methods. In the study, the following substances were used: cinnarizine, PLGA (50:50), polyvinyl alcohol (PVA). The remaining reagents and solvents fitted into the category of chemically pure. For development of the methods for quantitative determination of cinnarizine and its validation, a spectrophotometric method of analysis was used. Model mixtures used as objects of the study, had been prepared. Validation assessment of the methods was carried out upon such indicators as specificity, linearity, detection limit, repeatability, reproducibility.

Results

Results. Methods for spectrophotometric determination of the degree of cinnarizine inclusion has been developed. It has been established that encapsulation reaches 63.74%. Validation testing methods has been carried out. The results of such tests as specificity, linearity, detection limit, repeatability, reproducibility correspond to the safe range of values regulated by Product specification file. Due to the impossibility of determining the degree of cinnarizine inclusion on the basis of standard methods of preparation, the technology of producing nanocapsules has been adjusted.

Conclusion

Conclusion. The technology has been optimized and new techniques have been developed. Taking into account the characteristics of production and the physicochemical properties of the components, they make a reliable analysis of the degree of cinnarizine inclusion in nanocapsules possible. The relative error of the developed methods of determination does not exceed ± 2.67%. Based on the results of the validation assessment, this methods is valid for all indicators. 

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The authors declare that there are no conflicts of interest present.