(306g) Surface Characterization of Aspirin Crystal Planes in the Presence of Polymers, Surfactants, and Solvents

In this work, a combination approach of molecular simulations in conjunction with experiments has been performed to study the interaction of non-ionic surfactant molecules with the major surfaces of model drug in the presence of polar (ethanol) and non-polar (toluene) solvents. The Poloxamer series of surfactants was chosen as a common non-ionic surfactant; several types of poloxamer were tested both experimentally and computationally to determine the impact of hydrophobicity and size of the additives on the growth of the crystals. In order to determine the effect of surfactants, the relative interfacial binding energies of the surfactant molecules with respect to each crystal surface were calculated for various surfactant molecules using a series of molecular dynamics simulations. Simulations were conducted using two solvents, ethanol and toluene, on three growth planes ((001), (010), and (100) faces) of the aspirin crystal. Experimental validation was conducted by a series of recrystallization experiments containing identical molar concentrations of the desired surfactants. It was found the hydrogen bonding plays a crucial role in the stabilization of the drug. In addition, it was found that the smaller, more hydrophobic Poloxamer series surfactants, such as Poloxamer 101, displayed the most significant interfacial binding energy, indicating a more significant interaction; these results were confirmed experimentally. It was also found that the non-ionic surfactants were more influential on the crystallization when a non-polar solvent was used. Furthermore, it was discovered that the non-ionic Poloxamer series of surfactants have a tendency to affect the crystal surfaces evenly, which results in an overall quenching of the crystal growth and a more uniform plate-like morphology of the resulting crystals. The significant effect on the surface of the crystal indicates that the Poloxamer series are the most effective stabilizers for the aspirin crystal and similar drug crystallizations of those tested. A model for the prediction of morphology was proposed and morphologies were confirmed experimentally. Finally, the findings were compared with the use of more common non-ionic surfactants Tween 80 and Tyloxapol, where it was discovered that the Poloxamer series was significantly more effective.