Purpose: The commonly used anionic surfactant, sodium lauryl sulfate (SLS), is known to deteriorate the dissolution of some drugs through forming poorly soluble drug-LS salts. The aim of this research was to investigate the prevalence of such phenomenon, develop the precipitation rules that can be used to guide the appropriate use of SLS in drug development. Methods: Drug molecules containing cationic groups (such as salt of basic drugs or quaternary ammonium salt) or basic groups that can be positively charged in an acidic environment were selected. To study pH effect on the formation of lauryl sulfate (LS-) salt, drug and SLS were dissolved in water at a pH above the pKa of the drug. The solution pH was reduced by adding concentrated HCl solution while the occurrence of precipitation was monitored closely. To investigate the role of solubility product (Ksp) of the drug lauryl sulfate salt, the Ksp was calculated from concentration of drug and LS- in deuterated water saturated by the salt by NMR. Solutions with a range of ion products (Q) of drug cation and LS- were prepared by varying concentrations of drug and LS- at pH 1.2. The samples were then observed for signs of precipitation. The effect of micelle formation of SLS on precipitation of the lauryl sulfate salt was also studied by introducing different amount of SLS into the drug solution at a low pH. Results: A total of 13 out of 18 compounds investigated formed poorly soluble drug lauryl sulfate salt and precipitated out. Results showed that both low pH, which is a prerequisite for the protonation of drug molecules, and Q > Ksp are required for the precipitation of drug lauryl salts. However, the SLS concentration should not surpass its CMC in an effort to increase Q. Otherwise, precipitation does not occur, as any precipitation would have been solubilized by the SLS micelles. Conclusion: The prevalence of the formation of poorly soluble drug lauryl salt highlights the need to exercise caution when using SLS in drug development. The incorporation of SLS in a solid formulation as a wetting agent may actually slow down the dissolution of drugs. If SLS is used in dissolution medium, the dissolution of a drug from the formulation may be erroneously characterized as too slow when it may have been excellent in a SLS free in vivo environment. The rules developed in this study can be implemented to guide the use of SLS in formulation development of a basic drug by avoiding unexpected problems during dissolution.