Pharmaceutical Lauryl Sulfate Salts: Prevalence, Formation Rules, and Formulation Implications

The anionic surfactant sodium lauryl sulfate (SLS) is known to deteriorate the dissolution of some drugs by forming poorly soluble lauryl sulfate (LS) salts. However, because of the perception of its infrequent occurrence, this phenomenon is usually not investigated in drug development until unexpected dissolution slowdown is encountered. This work demonstrates the prevalence of this phenomenon, where 14 out of 18 compounds with diverse chemical structures, including salts of basic drugs, a quaternary ammonium salt, organic bases, and zwitterionic molecules, precipitated from a solution when mixed with SLS. Although no precipitation was observed for the other 4 compounds, their FTIR spectra suggested 3 of them had intermolecular interactions with SLS when dried from a solution. These results, along with the 5 other examples reported in the literature, demonstrate the prevalence of this phenomenon. The occurrence of precipitation is thermodynamically driven by the relative difference between the ion product in solution (Q) and the solubility product of the lauryl sulfate salt (Ksp). SLS, as a surfactant, also affects precipitation kinetics by influencing the interfacial tension of nuclei of the insoluble salt. When a potential issue associated with the LS salt is identified, effective mitigation strategies should be proactively designed and implemented to alleviate its possible negative impact on drug dissolution.