pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2026-14-2-201-213pmedpharm-1871Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEРазработка состава и технологии получения мини-таблеток пропранолола гидрохлорида с применением подхода «качество через проектирование»Development of the Composition and Technology for Obtaining Mini-Tablets of Propranolol Hydrochloride Using the Quality by Design Approachhttps://orcid.org/0009-0005-2916-3756НовиковЯ. С.NovikovYa. S.

аспирант Института фармации ФГБОУ ВО Казанский ГМУ Минздрава России. 

Россия, 420012, г. Казань, ул. Бутлерова, д. 49.

 

postgraduate student of the Institute of Pharmacy, Kazan State Medical University. 

49 Butlerov Str., Kazan, Russia, 420012.

voilt01-12@mail.ruhttps://orcid.org/0009-0006-7232-0056УрясоваМ. Д.UryasovaM. D.

ординатор Института фармации ФГБОУ ВО Казанский ГМУ Минздрава России. 

Россия, 420012, г. Казань, ул. Бутлерова, д. 49.

 

resident of the Institute of Pharmacy, Kazan State Medical University. 

49 Butlerov Str., Kazan, Russia, 420012.

mashenka21.01.2000@mail.ruhttps://orcid.org/0000-0001-7671-3179ЕгороваС. Н.EgorovaS. N.

доктор фармацевтических наук, профессор, заместитель директора по образовательной деятельности Института фармации ФГБОУ ВО Казанский ГМУ Минздрава. 

Россия, 420012, г. Казань, ул. Бутлерова, д. 49.

Doctor of Sciences (Pharmacy), Professor, Deputy Director for Educational Activities of the Institute of Pharmacy, Kazan State Medical University. 

49 Butlerov Str., Kazan, Russia, 420012.

svetlana.egorova@kazangmu.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Казанский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияKazan State Medical University.Russian Federation202629042026142201213Copyright © Новиков Я.С., Урясова М.Д., Егорова С.Н., 20262026Новиков Я.С., Урясова М.Д., Егорова С.Н.Novikov Y.S., Uryasova M.D., Egorova S.N.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/1871

Инфантильная гемангиома (ИГ) представляет собой доброкачественное сосудистое новообразование, встречающееся у 4–10% новорождённых и требующее своевременной терапии при осложнённом течении. На сегодняшний день пропранолол признан «золотым стандартом» лечения ИГ благодаря доказанной эффективности и безопасности. Однако в Российской Федерации отсутствуют доступные лекарственные формы (ЛФ) пропранолола для детей, что создает значительную проблему для педиатрической практики. В связи с этим актуальна разработка ЛФ, обеспечивающей точность дозирования и удобство применения у детей.

Цель

Цель. Разработка состава и технологии получения ородиспергируемых мини-таблеток (ОДМТ) пропранолола гидрохлорида для детей с использованием подхода «качество через дизайн» (Quality by Design, QbD).

Материалы и методы

Материалы и методы. Для достижения цели исследования использовали активную фармацевтическую субстанцию пропранолола гидрохлорида и вспомогательные вещества: маннитол, микрокристаллическая целлюлоза 102 (МКЦ 102), кросповидон (КПВ), натрия сахарината дигидрат, натрия стеарилфумарат (НСФ) и кремния диоксид коллоидный. Разработку состава проводили с использованием методологии QbD, планирование эксперимента методом Mixture Design (MD). Независимыми переменными выступали содержание МКЦ 102, КПВ и НСФ. ОДМТ диаметром 3 мм получали прямым прессованием. Таблеточную смесь и ОДМТ испытывали по методикам, представленным в Государственной фармакопее Российской Федерации XV издания: сыпучесть, насыпная плотность и плотность после уплотнения, прочность на раздавливание, истираемость, распадаемость, однородность массы. Однородность дозирования оптимизированного состава определяли методом ВЭЖХ.

Результаты

Результаты. На первом этапе определили целевой профиль качества ОДМТ. В соответствии с ним установлены критические показатели качества (КПК): для порошковой смеси — сыпучесть, насыпная плотность, плотность после уплотнения; для ОДМТ — прочность на раздавливание, распадаемость, истираемость и однородность дозирования. Разработан и оптимизирован состав, позволивший достичь требуемых значений всех КПК. В ходе статистического анализа выявлены значимые межкомпонентные взаимодействия, влияющие на прочность и распадаемость ОДМТ.

Заключение

Заключение. Разработан состав и технология получения ОДМТ пропранолола гидрохлорида.

Infantile hemangioma (IH) is a benign vascular neoplasm, occurring in 4–10 % of newborns and requiring timely therapy in cases of complicated progression. Currently, propranolol is recognized as the "gold standard" for IH treatment due to its proven efficacy and safety. However, in the Russian Federation, there are no readily available dosage forms (DFs) of propranolol for children, which creates a significant problem for pediatric practice. In this regard, the development of a PF that ensures accurate dosing and ease of use in children is relevant.

The aim

The aim. To develop the composition and technology for obtaining orodispersible mini-tablets (OMT) of propranolol hydrochloride for children using the Quality by Design (QbD) approach.

Materials and methods

Materials and methods. The active pharmaceutical substance of propranolol hydrochloride and excipients were used: mannitol, microcrystalline cellulose 102 (MCC 102), crospovidone (CPV), sodium saccharin dihydrate, sodium stearyl fumarate (SSF), and colloidal silicon dioxide. The composition development was carried out using the QbD methodology, with experimental design planned using the Mixture Design (MD) method. The independent variables were the content of MCC 102, CPV, and SSF. OMT with a diameter of 3 mm were obtained by direct compression. The tablet blend and OMT were tested according to the methods presented in the State Pharmacopoeia of the Russian Federation, XV edition: flowability, bulk density and tapped density, crushing strength, friability, disintegration, and mass uniformity. The dose uniformity of the optimized composition was determined by HPLC.

Results

Results. During the first stage, the target quality profile of the OMT was determined. In accordance with this, critical quality attributes (CQAs) were established: for the powder blend  – flowability, bulk density, tapped density; for the OMT – crushing strength, disintegration, friability, and dose uniformity. A composition was developed and optimized, which allowed the required values for all CQAs to be achieved. Statistical analysis revealed significant inter-component interactions affecting the crushing strength and disintegration of the OMT.

Conclusion

Conclusion. The composition and technology for obtaining orodispersible mini-tablets of propranolol hydrochloride have been developed.

пропранолола гидрохлоридмини-таблеткиородиспергируемые формыкачество через дизайнинфантильная гемангиомаpropranolol hydrochloridemini-tabletsorodispersible formsQuality by Designinfantile hemangiomaФармацевтическая субстанция пропранолола гидрохлорида и все вспомогательные вещества были предоставлены АО «Татхимфармпрепараты». Растворители для ВЭЖХ, хроматографическая колонка и стандартный образец пропранолола гидрохлорида были приобретены в рамках программы Приоритет-2030.The propranolol hydrochloride and all excipients were provided by JSC Tathimpharmparaty. Solvents for HPLC, a chromatographic column, and a standard sample of propranolol hydrochloride were purchased under the Priority 2030 Program.ReferencesHolm A., Mulliken J.B., Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor // J Clin Invest. – 2024. – Vol. 134, No. 8. – P. e172836. DOI: 10.1172/JCI172836Holm A, Mulliken JB, Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. 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The authors declare that there are no conflicts of interest present.