Comparative Study of Methods for the Pharmaceutical Preparation and Effectiveness of Darunavir Ethanolate Compositions with Mesoporous Carriers and Polymer Solid Dispersions

Purpose
The aim of this work was to study the effectiveness of various methods for improving the solubility and bioavailability of darunavir by mesoporous carriers and water-soluble polymers in the form of amorphous solid dispersions.

Methods
Preliminarily, using the solvent wetting method, solid dispersions with various water-soluble polymers were obtained, which were tested for the presence of amorphism by X-ray diffraction and scanning electron microscopy methods and to determine the leader in increasing the solubility of darunavir. The selected polymer became the basis for the formulations, which were separately obtained by industrially available hot-melt extrusion and spray-drying methods, mixed with needful excipients and compressed to form dispersible tablets. The resulting tablets were tested in vitro using a dissolution test and in vivo for bioavailability in minipigs.

Results
Of all tested polymer dispersions, the best solubility results have been shown with Eudragit EPO systems for solvent wetting, hot melt extrusion, and fluidized bed methods. These compositions became the basis of polymer formulations that showed better dissolution compared to physical mixture on a mesoporous carrier without polymer. The bioavailability test revealed the highest efficacy of the polymer dispersion on the mannitol particles.

Conclusion
All formulations obtained, containing various solid dispersions, performed better than the original Prezista. This observation allows us to take further steps to reduce the drug load.

Zolotov, S.A., Demina, N.B., Dain, I.A. et al. Comparative Study of Methods for the Pharmaceutical Preparation and Effectiveness of Darunavir Ethanolate Compositions with Mesoporous Carriers and Polymer Solid Dispersions. J Pharm Innov (2022).
https://doi.org/10.1007/s12247-022-09667-5

excipients formulation