Crystallographic and Energetic Insights into Reduced Dissolution and Physical Stability of a Drug-Surfactant Salt: The Case of Norfloxacin Lauryl Sulfate.

Abstract

A commonly used pharmaceutical surfactant, sodium lauryl sulfate (SLS), has been reported to reduce the dissolution rate of drugs due to the formation of a less soluble drug-lauryl sulfate salt. In this study, we provide direct crystallographic evidence of the formation of salt between SLS and norfloxacin (NOR), [NORH+][LS-]·1.5 H2O. The available crystal structure also enables the use of the energy framework to gain an understanding of the structure-property relationship. Results show that the hydrophobic methyl groups in SLS dominate the surfaces of the [NORH+][LS-]·1.5 H2O crystals, resulting in the increased hydrophobicity and reduced wettability by aqueous media. Moreover, an analysis of molecular environments and energy calculations of water molecules provides insight into the stability of [NORH+][LS-]·1.5 H2O with variations in the relative humidity and temperature. In summary, important pharmaceutical properties, such as solubility, dissolution, and thermal stability, of the drug-surfactant salt [NORH+][LS-]·1.5 H2O have been characterized and understood based on crystallographic and energetic analyses of the crystal structure.