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

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 HO. 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 HO 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 HO 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 HO have been characterized and understood based on crystallographic and energetic analyses of the crystal structure.