Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate

Sodium lauryl sulfate (SLS) is an anionic surfactant widely used in pharmaceutical research as a dissolution enhancer for poorly soluble drugs. When SLS was used in ritonavir (RTV) tablet formulation to improve wetting, dissolution of RTV was surprisingly deteriorated in acidic media. To understand this unexpected phenomenon, a systematic investigation, including solubility determination, intrinsic dissolution rate measurement, dissolution in an artificial stomach and duodenum apparatus, and solid-state characterization, revealed the formation of a poorly soluble salt, [RTV ²⁺ ][LS ⁻ ] ₂ , in an acidic environment. Solubilization of the poorly soluble RTV salt was observed when the concentration of SLS exceeded the critical micelle concentration. Thus, precipitation of [RTV ²⁺ ][LS ⁻ ] ₂ at a low pH and in presence of a low SLS concentration can lead to deteriorated bioavailability. This unintended negative effect on dissolution should be carefully considered when using SLS in a tablet formulation of a basic drug that can be ionized in gastric fluid.