Effect of particle size on release of solid dispersed particles during the "Dissolution" test

Introduction. The use of the solid disperse systems method to increase the solubility of lipophilic active pharmaceutical ingredients is industrially applicable using different technologies, but the influence of particle size on the dissolution of these systems, depending on the method, is not sufficiently reflected in the literature. Aim. To study the influence of the particle size of amorphous solid disperse systems "darunavir-water-soluble polymer" obtained by solvent removal and hot melt extrusion on the dissolution of Darunavir in the biological pH range of 1.2; 4.5 and 6.8. Materials and methods. Amorphous solid disperse systems were obtained in two ways: solvent removal and hot melt extrusion. Amorphism was determined by X-ray powder diffraction and electron microscopy. The efficiency of disperse systems was compared based on the results of the "Dissolution" test of powders mechanically ground to the same particle size in the biological pH range. The concentration of Darunavir in solution was determined using high-performance liquid chromatography with diode array detection. Results and discussion. The best result was shown by a solid dispersion system based on the Eudragit® E PO polymer with a particle size D 90 of less than 10 μm. The increase in the concentration of Darunavir relative to the crystalline form corresponding to Darunavir ethanolate was 324, 2485, and 740%, respectively, in dissolution media with pH 1.2; 4.5, and 6.8. Conclusions. Methods for obtaining solid dispersion systems, such as solvent removal and hot melt extrusion with the same particle size, do not affect the concentration of the Darunavir API in solution in the biological pH range during the Dissolution test.