Among the newly discovered active ingredients, as many as 70 % of them are practically insoluble in water. This is the reason why scientists use a variety of approaches to increase their solubility, which is needed for their use in practice. One of these approaches is also melt granulation, which we performed in a high-shear mixer as part of our research work. The main ingredient for successful granulation is binder that melts or softens at increased temperatures. The binder must have a melting point between 50 and 100 °C. They are divided into two groups: hydrophilic and hydrophobic. In our research, we focused on hydrophilic binders, which are suitable for the manufacture of immediate release delivery systems.
The purpose of the Master's Thesis was to improve the water solubility of the model active ingredient carvedilol, which according to the biopharmaceutical classification system belongs to group II. In a combination with different hydrophilic binders and mesoporous carriers, we produced granules in a high-shear mixer with melt granulation. We wanted granules that would increase the solubility of carvedilol as much as possible, and at the same time show good flow properties. Granulation was performed with 6 different carriers (Avicel® PH 101, Fujicalin® SG, Neusilin® US2, Syloid® 244 FP, Syloid® XDP 3050, Aeroperl® 300) and 7 different binders (PEG 6000, poloxamer 188, Gelucire® 48/16, Gelucire® 50/13, and 4 sugar esters D-1216, D-1615, D-1616, D-1816).
The best flow properties and the best release profiles were achieved with granules made using the carrier Neusilin® US2 and binder Gelucire® 50/13. These had better flow properties than granules prepared with carrier Avicel® PH 101, which is mainly due to the shape of the latter. Using a scanning electron microscope, we confirmed that they are irregular in shape and with sharp edges, while the granules made of Neusilin® US2 were round and compact, which was the reason for their good flow time and good Carr index. The granules produced using 15 % sugar ester addition, showed a more porous structure and rough surfaces. With differential scanning calorimetry we confirmed the conversion of the carvedilol from a crystalline to an amorphous form, which is desirable since such a form is more soluble. In future studies, it would be good to study the stability of the amorphous carvedilol, as the mesoporous carriers which we used in our research work represent one of the established approaches for the stabilization of amorphous forms of active ingredients.
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