Improving the solubility of poorly water soluble active pharmaceutical ingredients that according to the biopharmaceutical classification system belong to class II is one of the main challenges pharmaceutical industry is facing nowadays. One of the drugs belonging to that group is nonsteroidal anti-inflammatory drug naproxen. We aimed to improve its solubility by making its solid dispersions in mesoporous silica.
We used three different methods to prepare the solid dispersions – two solvent evaporation methods (rotavapor evaporation and immersion method) and the melt method, in which we used an infrared heater. Additionally, we used different proportions of mesoporous silica produced by two manufacturers – Parteck® SLC 500 and Syloid® XDP 3150.
Our first aim was to determine which of the three methods was optimal regarding its repeatability, economy and how the molecules were loaded into the carrier. We assessed the latter by performing thermal analysis. Our conclusion was that the melt – infrared heater – method is in many ways better than the methods in which organic solvents are used.
Secondly, we used differential dynamic calorimetry to analyze solid dispersions prepared by evaporating the solvent by the rotavapor. We analyzed freshly prepared dispersions and the dispersions that had been kept in accelerated stability test conditions for 6 weeks. Our conclusion was that with time there is an increasing amount of amorphous form of naproxen, which might be due to the spontaneous amorphization of the drug.
Finally, we produced rapidly disintegrating tablets from the solid dispersions containing 20% and 30% of naproxen and tested how the drug was released in 0,1 M HCl solution. We analysed the release profiles of the samples, in the making of which we used various process parameters of tableting, different amounts of active ingredient, methods of preparation and two mesoporous carriers with different properties. We found out that there are numerous factors that affect the speed and rate of release. Those factors are the hardness of the formulation, the amount of active ingredient in it, the method we used to prepare solid dispersions and the properties of used mesoporous carriers. We can conclude that the formulations with solid dispersions had improved release when compared to physical mixtures and that the most optimal release profile belonged to the formulation containing 20% solid dispersion prepared with the melt method.
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