Investigating Eutectic Mixtures for Poorly Soluble Compounds By

Improving the solubility and changing the dissolution rate of the poorly soluble active pharmaceutical ingredients (API’s) AMG 517, glipizide, and naproxen through the preparation of eutectic mixtures was investigated. Mixtures of the API’s with other small molecules were prepared to construct a phase diagram used to identify the eutectic mixture compositions. The search for a eutectic mixture in a co-crystal phase diagram was investigated by mixing AMG 517 with known co-crystal formers sorbic acid and trans-cinnamic acid. Glipizide was mixed with a series of amides to investigate the presence of eutectic mixtures, but the thermal instability of the API was such that chemical degradation overwhelmed any other thermal transitions. A phase diagram of naproxen and vanillin was prepared and the composition of the eutectic mixture identified. The eutectic mixture at 0.11 MF naproxen vanillin (11% naproxen/ 89% vanillin) was found to have a melting point of 75 oC. The melt is reversible and thermally stable, as tested by multiple melts and coolings. Further studies are planned to evaluate whether the eutectic mixture may be advantageous to develop. However, expectations are modest due to the small amount of naproxen present in the eutectic mixture.