Thermal analytical techniques used in the characterization of pharmaceutical eutectics

摘要

Enhancement of the dissolution rates of slightly soluble aspirin, phenacetin and naproxen, andinsoluble ketoconazole and indomethacin were investigated. Solid dispersions were prepared by the solventmethod and characterized by differential scanning calorimetry. Phase diagrams were constructed andeutectics were found containing 40% aspirin-60% PEG, 20% ketoconazole-80% urea, 32.5% phenacetin-67.5% ketoconazole, 40% aspirin-60% indomethacin, 40% phenacetin-60% indomethacin, 50% aspirin-50% naproxen and 50% phenacetin-50% naproxen (w/w). Hot stage microscopic observationscorroborated the DSC results with a single solid to liquid transition around the same eutectic meltingtemperatures. Powder x-ray diffraction analysis revealed that the eutectics are crystalline, and thereforestable. Optical photomicrographs of the samples revealed that there was a marked reduction in particlesize of the minor components providing a greater surface area present for dissolution, and dissolutionprofiles for the aspirin-PEG and ketoconazole-urea eutectics showed enhancement in their dissolutionrates. The results indicate that eutectic formation is a valuable option for improving the dissolution rateand greatly enhancing the bioavailability of poorly water-soluble drugs.