pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2025-13-4-260-269pmedpharm-1709Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEОценка возможных рисков на этапе фармацевтической разработки мини-таблетокAssessment of potential risks at the pharmaceutical development stage of minitabletshttps://orcid.org/0009-0005-2916-3756НовиковЯ. С.NovikovYa. S.

ассистент Института фармации, ФГБОУ ВО Казанский ГМУ Минздрава России. 

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

Assistant at the Institute of Pharmacy, Kazan State Medical University.

49, Butlerova str., Kazan, Russia, 420012.

yaroslav.novikov@kazangmu.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 России. 

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

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

49, Butlerova str., Kazan, Russia, 420012.

svetlana.egorova@kazangmu.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Казанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKazan State Medical University.Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Казанский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияKazan State Medical University.Russian Federation202504092025134260269Copyright © Новиков Я.С., Егорова С.Н., 20252025Новиков Я.С., Егорова С.Н.Novikov Y.S., 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/1709

Производство  мини-таблеток (МТ) значительно отличается от выпуска таблеток обычного размера и сопряжено с определёнными рисками. В статье проведён анализ научных публикаций на тему разработки и производства МТ, и на основе полученных данных оценены связанные с этим риски.

Цель

Цель. Провести оценку рисков при фармацевтической разработке МТ.

Материалы и методы

Материалы и методы. В качестве материалов исследования за основу были взяты руководства по фармацевтической разработке ICHQ8 и управлению рисками для качества ICHQ9, рекомендации Государственной фармакопеи РФ xv издания, научные публикации по фармацевтической разработке и производству МТ. Исследование проводили методом РНА (предварительного анализа опасностей). В качестве критических показателей качества (КПК) МТ были рассмотрены: распадаемость, растворение, однородность дозирования, однородность массы, прочность на раздавливание, истираемость. Идентификация опасностей проводилась методом построения диаграммы Исикавы. Анализ рисков проводился на основании данных научных публикаций на тему разработки и производства МТ. Поиск статей осуществлялся за период с 1990 по 2024 год в базах данных ScienceDirect, PubMed, Академия Google и elibrary.ru. На основании сведений, представленных в этих статьях, и логическим методом были определены вероятность возникновения и тяжесть (последствия) рисков. Оценивание рисков проводилось с использованием матрицы рисков.

Результаты

Результаты. Среди параметров технологического процесса производства МТ представляют опасность стадии прессования и смешивания. Прессование связано с высоким риском для следующих КПК: растворение, однородность дозирования, однородность массы и прочность МТ на раздавливание. Смешивание критически важно для обеспечения однородности дозирования. Параметры активной фармацевтической субстанции (АФС), такие как размер и форма частиц, существенно влияют на растворение. Кроме того, прессуемость и сыпучесть АФС являются рискообразующими факторами для обеспечения однородности дозирования и массы МТ. Огромное значение при разработке МТ имеет выбор вспомогательных веществ (ВВ). Наибольший риск воздействия на изучаемые КПК представляет тип и содержание наполнителя. Нерациональный выбор дезинтегранта и антифрикционного ВВ может привести к нарушению распадаемости и растворения МТ.

Заключение

Заключение. В результате оценки рисков были идентифицированы опасности, проанализированы и оценены ключевые риски, связанные с фармацевтической разработкой МТ. Особое внимание было уделено основным группам опасностей — влиянию свойств АФС, ВВ и параметрам производственного процесса на КПК МТ. Выявлено, что при разработке МТ особый риск представляет форма и размер частиц АФС, прессуемость и сыпучесть порошковой смеси, тип и содержание наполнителя и дезинтегранта, а также такие параметры технологического процесса, как прессование и смешивание.

The production of mini tablets (MTs) differs significantly from the production of regular-sized tablets and involves certain risks. The article analyzes scientific publications on the topic of MTs development and production, and based on the data obtained, assesses the risks associated with it.

The aim

The aim: To conduct a risk assessment during the pharmaceutical development of MTs.

Materials and methods

Materials and methods. The research materials were based on the ICHQ8 guidelines for pharmaceutical development and ICHQ9 guidelines for quality risk management, State Pharmacopoeia of the Russian Federation XV edition, scientific publications on the pharmaceutical development and production of MTs. The study was conducted using the PHA (preliminary hazard analysis) method. The following were considered as critical quality attributes (CQAs) of MTs: disintegration, dissolution, uniformity of dosage units, uniformity of mass, crushing strength, and friability. Hazards were identified using the Ishikawa diagram method. Risk analysis was performed based on data from scientific publications on the development and production of MTs. Articles were searched for between 1990 and 2024 in the ScienceDirect, PubMed, Google Scholar, and elibrary.ru databases. Based on the information presented in these articles and using a logical method, the probability of occurrence and severity (consequences) of the risks were determined. Risk assessment was carried out using a risk matrix.

Results

Results. Among the parameters of the MTs production process, the compression and mixing stages pose a danger. The compression is associated with a high risk for the following CQAs: dissolution, uniformity of dosage units, uniformity of mass, and crushing strength. Mixing is critical to ensuring dosage uniformity. Parameters of the active pharmaceutical ingredient (API), such as particle size and shape, significantly affect dissolution. In addition, the compressibility and flowability of the API are risk factors for ensuring the uniformity of dosage and MTs mass. The choice of excipients (EPs) is of great importance in the development of MTs. The type and content of the filler are of the greatest risk to the studied MTs. An irrational choice of disintegrant and anti-friction EPs can lead to impaired disintegration and dissolution of MTs.

Conclusion

Conclusion. As a result of the risk assessment, hazards were identified, and key risks associated with the pharmaceutical development of MTs were analyzed and evaluated. Particular attention was paid to the main groups of hazards — the influence of the properties of API, EPs, and production process parameters on MTs CQAs. It was found that during the development of MTs, the shape and size of the API particles, the compressibility and flowability of the powder mixture, the type and content of the filler and disintegrant, as well as such technological process parameters as pressing and mixing, pose a particular risk.

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