Development of novel darunavir amorphous solid dispersions with mesoporous carriers

• Published in: European journal of pharmaceutical sciences 2021-04, Vol.159, p.105700-105700, Article 105700
• Main Authors: Zolotov, Sergey A., Demina, Natalia B., Zolotova, Anna S., Shevlyagina, Natalia V., Buzanov, Grigorii A., Retivov, Vasilii M., Kozhukhova, Evgeniia I., Zakhoda, Oleg Y., Dain, Igor A., Filatov, Andrei R., Cheremisin, Alexander M.
• Format: Article
• Language: English
• Subjects: Amorphous solid dispersion; Darunavir; Differential scanning calorimetry; Dissolution testing; Magnesium aluminum silicate; Mesoporous silica; X-ray powder diffraction
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.105700

The aim of this work was to compare mesoporous carriers based on silica and magnesium aluminosilicate in the amorphous solid dispersion production. Darunavir has been selected as an active pharmaceutical ingredient that is classified as a Class 2 BCS substance and exists in two commercially available forms: crystalline ethanolate and amorphous. In the course of the study, the conditions for the preparation of amorphous samples with the selected carriers were evaluated within the framework of the most common methods for obtaining solid dispersions - hot-melt extrusion, solvent wetting, and spray drying. It was determined that the obtained dispersion properties almost completely repeat the properties of the corresponding carriers. The resulting dispersions were examined in a dissolution test and the best ones was used to formulate tablets, which were studied in an in vitro dissolution test with the original Prezista. The proposed tablet formulation showed improved dissolution compared to the original one. It was also found that silica supports have a greater positive contribution to darunavir dissolution - both ethanolate or amorphous forms. [Display omitted]