The development of a weakly basic compound is often challenging due to changes in pH\nthat the drug experiences throughout the gastrointestinal tract. As the drug transitions from the\nlow pH of the stomach to the higher pH of the small intestine, drug solubility decreases. A stomach\nwith a higher pH, caused by food or achlorhydric conditions brought about by certain medications,\ndecreases even the initial solubility. This decreased drug solubility is reflected in lower in vivo\nexposures. In many cases, a solubility-enabling approach is needed to counteract the effect of\ngastrointestinal pH changes. Solid dispersions of amorphous drug in a polymer matrix have been\ndemonstrated to be an effective tool to enhance bioavailability, with the potential to mitigate the\nfood and achlorhydric effects frequently observed with conventional formulations. Because solid\ndispersions are in a metastable state, they are particularly sensitive to processing routes that may\ncontrol particle attributes, stability, drug release profile, and bioperformance. A better understanding\nof the impacts of processing routes on the solid dispersion properties will not only enhance our ability\nto control the product properties, but also lower development risks. In this study, a weakly basic\ncompound with greatly reduced solubility in higher pHs was incorporated into a solid dispersion\nvia both spray drying and hot melt extrusion. The properties of the solid dispersion via these two\nprocessing routes were compared, and the impact on dissolution behavior and in vivo performance\nof the dispersions was investigated.
Loading....