pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2020-9-3-45-50pharmjournal-831Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯPHARMACEUTICAL TECHNOLOGYИзучение высвобождения галоперидола из поликомплексных наночастиц на основе сополимеров Eudragit®А Study of Haloperidol Release from Polycomplex Nanoparticles Based on Eudragit® Copolymershttps://orcid.org/0000-0002-7110-2093ПорфирьеваН. Н.PorfiryevaN. N.

420126, Республика Татарстан, Казань, ул. Фатыха Амирхана, д. 16.

Natalia N. Porfiryeva.

https://orcid.org/0000-0002-7221-2630ХуторянскийВ. В.KhutoryanskiyV. V.

420126, Республика Татарстан, Казань, ул. ФатыхаАмирхана, д. 16;

Whiteknights, PO box 224, Reading RG66AD.

Vitaliy V. Khutoryanskiy.

16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126; Whiteknights, PO box 224, Reading RG66AD.

https://orcid.org/0000-0002-0916-2853МустафинР. И.MoustafineR. I.

Мустафин Руслан Ибрагимович.

420126, Республика Татарстан, Казань, ул. Фатыха Амирхана, д. 16.

Rouslan I. Moustafine.

16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126.

rouslan.moustafine@gmail.comИнститут фармации ФГБОУ ВО Казанский ГМУ Минздрава РоссииInstitute of Pharmacy, Kazan State Medical UniversityИнститут фармации ФГБОУ ВО Казанский ГМУ Минздрава России; Reading School of Pharmacy, University of ReadingInstitute of Pharmacy, Kazan State Medical University; Reading School of Pharmacy, University of Reading202028082020934550Copyright © Порфирьева Н.Н., Хуторянский В.В., Мустафин Р.И., 20202020Порфирьева Н.Н., Хуторянский В.В., Мустафин Р.И.Porfiryeva N.N., Khutoryanskiy V.V., Moustafine R.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/831Введение

Введение. Развивающимся направлением современной фармацевтической технологии является поиск полимерных носителей для разработки микро- и наноразмерных систем доставки лекарственных средств. Актуальным вопросом при этом остаётся поиск эффективных методов для исследования высвобождения из такого рода систем.

Цель

Цель. Провести исследование высвобождения модельного лекарственного средства (ЛС) галоперидола из поликомплексных наночастиц, полученных на основе интерполиэлектролитных комплексов (ИПЭК) различными методами.

Материалы и методы

Материалы и методы. Получены ИПЭК в виде наночастиц на основе полимеров фармацевтического назначения (Eudragit® EPO и Eudragit® L100-55). Размер получаемых поликомплексных наночастиц измеряли методом динамического светорассеяния с помощью Zetasizer Nano-ZS (Malvern Instruments, Великобритания). Изучение высвобождения галоперидола было проведено в среде имитирующей назальную жидкость с использованием вертикальной диффузионной ячейки Франца (PermeGear, США), а также модифицированным методом USP IV на тестере растворения DFZ II «Проточная ячейка» (ERWEKA GMBH, Германия).

Результаты и их обсуждение. При использовании вертикальной диффузионной ячейки Франца, по прошествии практически 2,5 часов, наблюдается статистически значимое увеличение высвобождение галоперидола из поликомплексных наночастиц в сравнении с контролем (раствор галоперидола). В тоже время высвобождение ЛС с использованием метода «Проточной ячейки» (USP IV) осуществить не удалось, ввиду, по всей видимости, эффекта кристаллизации галоперидола на поверхности диализных мембран в наноадаптерах Float-A-Lyzer® G2. Не увенчались успехом попытки устранить этот эффект и улучшить проницаемость мембраны по отношению к галоперидолу, добавлением поверхностно-активных веществ (твин-80) и усилителей проницаемости (ДМСО).

Заключение

Заключение. Оба метода, безусловно, являются перспективными для исследования высвобождения ЛС из наноразмерных носителей, однако в случае трудно растворимых ЛС, к которым относится и галоперидол, диффузионный метод с использованием вертикальной ячейки Франца оказался наиболее эффективным.

Introduction

Introduction. The development of polymer carriers for micro- and nanoscale drug delivery systems is an emerging area of modern pharmaceutical technology. One of the urgent needs in this area is the development of effective methods to study the drug release from these systems.

Aim

Aim. This work aimed to study the release of a model drug (MD) haloperidol from polycomplex nanoparticles prepared based on interpolyelectrolyte complexes (IPEC) using various methods.

Materials and methods

Materials and methods. IPECs were prepared in the form of nanoparticles based on pharmaceutical polymers (Eudragit® EPO and Eudragit® L100-55). Size distribution of these nanoparticles were determined using dynamic light scattering on Zetasizer Nano-ZS equipment (Malvern Instruments, UK). The release of haloperidol was studied in a medium simulating an artificial nasal fluid using a vertical Franz diffusion cell (PermeGear, USA) as well as a modified USP IV method in a flow-through cell apparatus (DFZ II, Erweka, Germany).

Results and discussion

Results and discussion. Statistically significant increase in the release of haloperidol from polycomplex nanoparticles in contrast with the control (haloperidol solution) is observed when using a vertical diffusion or Franz cell, after almost 2.5 hours. At the same time, it was not possible to study the release of drug using the flow-through cell method (USP IV), due, apparently, to the effect of crystallization of haloperidol on the surface of dialysis membranes in the Float-A-Lyzer® G2 nanoadapters. The attempts to eliminate this effect and to improve the membrane permeability to haloperidol by adding surfactants (tween-80) and penetration enhancers (DMSO) were not successful.

Conclusion

Conclusion. Both methods are promising for studying the release of drugs from nanosized carriers; however, in the case of using poorly-soluble drugs, including haloperidol, the diffusion method using a vertical Franz cell is effective.

поликомплексные носителинаночастицыгалоперидолвысвобождениеячейка Франца«Проточная ячейка»polycomplex carriersnanoparticleshaloperidolreleaseFranz cellflow-through cellИсследование выполнено при финансовой поддержке Российского научного фонда (научный проект № 20-65-46007). Авторы выражают благодарность компании ERWEKA GmbH за предоставленную возможность выполнения работы на приборе DFZ II «Проточная ячейка», а также компании Evonik Rohm GmbH за предоставление образцов сополимеров Eudragit®.The study was carried out with the financial support of the Russian Science Foundation (RSF) in the framework of research project № 20-65-46007 (to N.N.P., V.V.K. and R.I.M.). The authors are also grateful to ERWEKA GmbH for the opportunity to work on the Flow Through Cell Apparatus DFZ II, and also to Evonik Rohm GmbH for providing samples of Eudragit® copolymers.ReferencesKaldybekov D. B., Filippov S. K., Radulescu A., Khutoryanskiy V. V. 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The authors declare that there are no conflicts of interest present.