vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2026-16-3-280-292vedomostiregmed-889Research ArticleГЛАВНАЯ ТЕМА: ИННОВАЦИИ В ФАРМАЦЕВТИКЕ: ПУТЬ ОТ НАУЧНОЙ ИДЕИ К ТЕХНОЛОГИЧЕСКОМУ ЛИДЕРСТВУMAIN TOPIC: INNOVATION IN PHARMACEUTICS: FROM SCIENTIFIC IDEA TO TECHNOLOGICAL LEADERSHIPРазработка и оптимизация технологий производства твердых лекарственных форм с модифицированным высвобождением: обзор литературыDevelopment and Optimization of Manufacturing Technologies for Modified-Release Solid Dosage Forms: A Literature Reviewhttps://orcid.org/0009-0001-5340-6990МатянкинД. В.MatyankinD. V.

Матянкин Даниил Владимирович 

Автомобильный пр-д, д. 6, стр. 5, Москва, 109029 

Daniil V. Matyankin 

6/5 Avtomobilny Lane, Moscow 109029 

veterveter1900@yandex.ruhttps://orcid.org/0009-0000-5139-8539МатянкинаА. И.MatyankinаA. I.

Матянкина Анна Игоревна 

Автомобильный пр-д, д. 6, стр. 5, Москва, 109029 

Волгоградский пр-т, д. 42, к. 24, Москва, 109316 

Anna I. Matyankinа 

6/5 Avtomobilny Lane, Moscow 109029 

42/24 Volgogradsky Ave, Moscow 109316 

https://orcid.org/0009-0007-8611-4509СлавковД. С.SlavkovD. S.

Славков Дмитрий Сергеевич 

Автомобильный пр-д, д. 6, стр. 5, Москва, 109029 

Dmitry S. Slavkov 

6/5 Avtomobilny Lane, Moscow 109029 

https://orcid.org/0000-0003-3034-750XШпрахЗ. С.ShprakhZ. S.

Шпрах Зоя Сергеевна, д-р фарм. наук 

Каширское шоссе, д. 23, Москва, 115522 

Zoya S. Shprakh, Dr. Sci. (Pharm.) 

23 Kashirskoe Hwy, Moscow 115522 

Общество с ограниченной ответственностью «МАКИЗ-ФАРМА»РоссияMAKIZ-PHARMA LLCRussian FederationОбщество с ограниченной ответственностью «МАКИЗ-ФАРМА» ; Общество с ограниченной ответственностью «АМЕДАРТ»РоссияMAKIZ-PHARMA LLC ; AMEDART LLCRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Министерства здравоохранения Российской ФедерацииРоссияN.N. Blokhin National Medical Research Centre of OncologyRussian Federation202604072026163280292Copyright © Матянкин Д.В., Матянкина А.И., Славков Д.С., Шпрах З.С., 20262026Матянкин Д.В., Матянкина А.И., Славков Д.С., Шпрах З.С.Matyankin D.V., Matyankinа A.I., Slavkov D.S., Shprakh Z.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/889

ВВЕДЕНИЕ. Несмотря на широкое применение твердых лекарственных форм (ТЛФ) с модифицированным высвобождением (МВ), обобщающих работ, охватывающих полный цикл их разработки — от выбора технологической платформы до применения цифровых инструментов оптимизации, — в литературе выявлено немного. Имеющиеся публикации, как правило, рассматривают отдельные технологические платформы, не затрагивая вопросы цифровой оптимизации.ЦЕЛЬ. Систематизация и критическая оценка современных подходов к оптимизации технологии получения твердых лекарственных форм с модифицированным высвобождением и определение роли цифровых инструментов в повышении эффективности фармацевтической разработки.ОБСУЖДЕНИЕ. Анализ научных публикаций показал, что гидрофильные матрицы на основе гидроксипропилметилцеллюлозы (ГПМЦ) остаются ведущей платформой для разработки пролонгированных форм. Однако контроль высвобождения высокорастворимых субстанций требует комбинирования гидрофильных и гидрофобных полимеров. Осмотические системы обеспечивают pH-независимый профиль высвобождения, но их применение сопряжено с риском раздражения желудочно-кишечного тракта. Мультипартикулярные формы снижают вероятность непреднамеренного высвобождения всей дозы; при этом качество полимерного пленочного покрытия определяет воспроизводимость кинетики высвобождения. Экструзия горячего расплава в сочетании с 3D-печатью методом послойного наплавления (Fused Deposition Modeling, FDM) позволяет формировать заданный профиль высвобождения путем варьирования геометрии лекарственной формы. Установлено, что концепция встроенного качества (Quality by Design) и методы машинного обучения существенно сокращают объем экспериментальных работ, хотя проблемы интерпретируемости глубоких нейронных сетей и дефицит внешней валидации интеллектуальных моделей остаются нерешенными.ЗАКЛЮЧЕНИЕ. Матричные системы на основе ГПМЦ занимают лидирующее положение среди технологий пролонгированного высвобождения благодаря масштабируемости и предсказуемой кинетике, однако оптимальный выбор технологии получения твердых лекарственных форм с модифицированным высвобождением определяется физико-химическими свойствами субстанции и фармакокинетическим профилем. Применение методов планирования эксперимента при разработке ТЛФ с МВ и машинного обучения позволяет сократить число экспериментальных работ. Перспективное направление дальнейших исследований связано с разработкой интерпретируемых прогнозных моделей и адаптацией нормативной базы к лекарственным формам, получаемым аддитивными методами (трехмерной печатью).

INTRODUCTION. Despite the widespread use of solid dosage forms (SDFs) with modified release (MR), there is a paucity in the literature of comprehensive reviews covering the full development cycle — from selection of a technological platform to the application of digital optimization tools. Existing publications typically focus on individual technological platforms without addressing digital optimization.AIM. To systematically review and critically evaluate modern approaches to optimi­ zing the manufacturing technology for obtaining of modified-release solid dosage forms, and to determine the role of digital tools in enhancing the efficiency of pharmaceutical development.DISCUSSION. The analysis of scientific publications showed that hydrophilic matrices based on hydroxypropyl methylcellulose (HPMC) remain the leading platform for the development of prolonged-release formulations. However, controlling the release of highly soluble drugs requires combining hydrophilic and hydrophobic polymers. Osmotic systems provide a pH-independent release profile, but their use is associated with the risk of gastrointestinal irritation. Multiparticulate forms reduce the likelihood of unintentional release of dose dumping; in such systems, the quality of the polymer film coating governs the reproducibility of release kinetics. Hot-melt extrusion combined with 3D printing using fused deposition modeling (FDM) enables the creation of a desired release profile by varying the geometry of the dosage form. It has been established that the Quality by Design concept and machine lear­ ning methods substantially reduce the experimental workload, although challenges related to the interpretability of deep neural networks and the lack of external validation of predictive models remain unresolved.CONCLUSIONS. Matrix systems based on HPMC hold a leading position among prolonged-release technologies owing to their scalability and predictable kinetics; however, the optimal choice of technology for solid dosage forms with modified release is determined by the physicochemical properties of the substance and the pharmacokinetic profile. The application of design of experiments methods and machine learning in the development of MR SDFs can substantially reduce the number of laboratory experiments. A promising direction for future research lies in the development of interpretable predictive models and the adaptation of the regulatory framework to dosage forms produced by additive manufacturing (three-dimensional printing).

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