Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press148610.17650/1726-9784-2025-24-4-10-18REVIEWОБЗОР ЛИТЕРАТУРЫReview ArticleObtaining solid dispersions of active pharmaceutical ingredients under supercritical antisolvent conditions: features and prospects of the methodПолучение твердых дисперсий активных фармацевтических субстанций в условиях сверхкритического антирастворителя: особенности и перспективы методаhttps://orcid.org/0000-0003-2930-9397MarkeevVladimir B.МаркеевВ. Б.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0000-0001-8726-6407VinogradovVladimir P.ВиноградовВ. П.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0000-0002-2578-9437SedovaMaria K.СедоваМ. К.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0000-0002-8321-6952TishkovSergey V.ТишковС. В.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0000-0003-3506-9051AlekseevKonstantin V.АлексеевК. В.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0000-0002-9494-1332BlynskayaEvgenia V.БлынскаяЕ. В.
Russian Federation
markeev_vb@academpharm.ruhttps://orcid.org/0009-0004-3584-3742DorofeevVladimir L.ДорофеевВ. Л.
Russian Federation
markeev_vb@academpharm.ruFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesФГБНУ «Федеральный исследовательский центр оригинальных и перспективных биомедицинских и фармацевтических технологий»17122025244101806122024Copyright ©; 2025, Markeev V.B., Vinogradov V.P., Sedova M.K., Tishkov S.V., Alekseev K.V., Blynskaya E.V., Dorofeev V.L.Copyright ©; 2025, Маркеев В.Б., Виноградов В.П., Седова М.К., Тишков С.В., Алексеев К.В., Блынская Е.В., Дорофеев В.Л.2025Markeev V.B., Vinogradov V.P., Sedova M.K., Tishkov S.V., Alekseev K.V., Blynskaya E.V., Dorofeev V.L.Маркеев В.Б., Виноградов В.П., Седова М.К., Тишков С.В., Алексеев К.В., Блынская Е.В., Дорофеев В.Л.https://creativecommons.org/licenses/by/4.0https://bioterapevt.abvpress.ru/jour/article/view/1486

Background. The solubility of active pharmaceutical ingredients (API) in water is one of the main factors affecting their bioavailability. Various methods are used to improve solubilation, including micronization and the creation of solid dispersions. The use of the method of rapid expansion of supercritical fluids makes it possible to combine the positive properties of micronization and the creation of solid dispersions, however, most APIs are insoluble in the main compound used to create the fluid – carbon dioxide. For this reason, the method of crystallization under supercritical antisolvent (SAS) conditions has been developed, which makes it possible to micronization and create solid dispersions of compounds insoluble in carbon dioxide.

Aim. The analysis of modern achievements in the field of creating solid dispersions (SD) using an analogue of the method of rapid expansion of supercritical liquids – the SAS method, where the liquid is used as an anti-solvent, which significantly expands the possibilities of using this approach.

Results. The use of SAS technology to create SD makes it possible to improve the solubility of API by amorphizing it and ensuring solubility at a level above the equilibrium value. As a polymeric carrier in SD, polyvinylpyrrolidone and hydroxypropylmethylcellulose are mainly used, while as a surfactant, Pluronic® F-127 is employed, which represents a copolymer consisting of ethylene oxide and polypropylene units. Ethanol or methanol is often used as a solvent, including in a mixture with dichloroethane or methylene chloride.

Conclusion. Improving the solubility of API by creating a SD using the SAS method can significantly increase the kinetics of dissolution. Despite its relevance, the process of creating a TD using the SAS method is quite complex, depending both on the API, the polymers and surfactants used, as well as on the process parameters and characteristics, ranging from process temperature and pressure to the mass transfer rate and the shape of the reactor and nozzle.

Введение. Растворимость активных фармацевтических субстанций (АФС) в воде является одним из основных факторов, влияющих на их биодоступность. Для улучшения солюбилизации используют различные методы, в том числе микронизацию и создание твердых дисперсий. Применение метода быстрого расширения сверхкритических флюидов позволяет совместить положительные свойства данных подходов. Однако большинство АФС нерастворимы в основном соединении, используемом для создания флюида, – диоксиде углерода. По этой причине развитие получил метод кристаллизации в условиях сверхкритического антирастворителя (supercritical antisolvent crystallization, SAS), позволяющий микронизировать и создавать твердые дисперсии (ТД) для нерастворимых в диоксиде углерода соединений.

Цель исследования – анализ современных достижений в области создания ТД с аналогом метода быстрого расширения сверхкритических флюидов – метода SAS, в котором флюид используется в качестве антирастворителя, что существенно расширяет возможности использования данного подхода.

Результаты. Использование технологии SAS для создания ТД позволяет улучшить растворимость АФС за счет ее аморфизации и обеспечения растворимости на уровне выше равновесного значения. В качестве полимерного носителя в ТД используют в основном поливинилпирролидон и гидроксипропилметилцеллюлозу, а в качестве поверхностно-активного вещества – Pluronic® F-127, представляющий собой сополимер, состоящий из звеньев оксидов этилена и полипропилена. В роли растворителя часто применяют этанол или метанол, в том числе в смеси с дихлорметаном или метиленхлоридом.

Заключение. Улучшение растворимости АФС путем создания методом SAS ТД позволяет существенно улучшить кинетику растворения. Несмотря на свою актуальность, процесс создания ТД методом SAS является достаточно сложным, зависящим как от свойств АФС, используемых полимеров и поверхностно-активных веществ, так и от параметров и характеристик процесса, начиная от температуры и давления процесса и заканчивая скоростью массопереноса и формой реактора и сопла.

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