A large proportion of active pharmaceutical ingredients have inadequate physico-chemical properties. Among these, solubility is probably the most important. We know many different approaches to improve the solubility of active ingredients; one of them is making solid dispersions with a suitable excipient. Solid dispersions are delivery system where the active ingredient is dispersed in a solid carrier. A useful carrier of solid dispersions can be mesoporous silica, which, in addition to porosity, is characterized by a large specific surface area. Due to its large specific surface area, we can incorporate a larger amount of active ingredients into the carrier. Solid dispersions have proven to be a promising way to enhance dissolution of active ingredients that belong to the second class of the biopharmaceutical classification system. Characteristics of this class are poor solubility and good permeability through membranes. Fenofibrate is an antilipemic substance from the fibrate family, and it belongs to the second class of biopharmaceutical classification system.
In the study, we prepared solid dispersions of fenofibrate by the solvent evaporation method at reduced pressure with three different solvents, at two different temperatures and with five different component ratios. We wanted to determine how these variables affect the improvement of dissolution of the active ingredient in a medium that simulates gastric conditions. We also evaluated the specific surface area, amorphousness and physical stability of the solid dispersions. Syloid® 244 FP was used as a carrier of solid dispersions.
We discovered that the dissolution of fenofibrate is significantly improved by incorporating it into a mesoporous carrier. The choice of solvents and production temperatures is important for such enhancement. The best results were obtained with solid dispersions made with ethyl acetate, in which the solubility of fenofibrate is already very good, and with production at a higher temperature, which is also explained by higher solubility and consequently better incorporation into the pores of the carrier. These solid dispersions had the best release results, regardless of the component ratio. In case of the other solid dispersions made with the other two solvents; the release of the active ingredient decreased as its ratio increased. We also found out that the component ratio and the manufacturing temperature have a significant effect on the appearance of nanocrystals of the active ingredient in solid dispersions and that the manufactured solid dispersions are not physically stable.
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