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Browsing by Author "Guo, Yiwang"

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    Tablet Dissolution Deterioration by Sodium Lauryl Sulfate - Mechanism and Mitigation Strategies
    (2021-07) Guo, Yiwang
    Dissolution in gastrointestinal tract (GI tract) is critical for oral solid dosage forms, especially for drugs with poor solubility. Among the commonly used approaches, applications of surfactant have become a popular way to address the problem of slow dissolution of poorly soluble drugs. Sodium lauryl sulfate (SLS) is a surfactant commonly used as a wetting agent when concentration is below critical micelle concentration (CMC), or a solubilizer when concentration is above CMC, both are expected to enhance drug dissolution. However, this anionic surfactant can also readily interact with the positively charged cations in solution, to form a poorly soluble lauryl sulfate salt. This leads to unexpectedly reduced drug dissolution. Given the frequent application of SLS in drug products, understanding the mechanism is important to avoid surprises. The study was started by systematically investigating the case of ritonavir (RTV), which forms a poorly soluble amorphous [RTV2+][LS-]2 salt with SLS at a low pH, the ion-ion interaction between drug cation and lauryl sulfate anion (LS−), was further proved from an analysis of the single crystal structure of [NORH+][LS-] salt, in which proton transfer was clearly observed between NORH+ and LS-. For such an acid-base reaction, the prevalence of lauryl sulfate salt among other pharmaceutical compounds was investigated, using 18 chemicals with diverse molecular structures. To investigate the precipitation rules of the poorly soluble lauryl sulfate salts, p-aminobenzoic acid (PABA), which forms [PABAH+][LS-] salt with SLS, was chosen as the model compound. The thermodynamic driving force, as well as precipitation kinetics, are discussed. With that, two formulation strategies were proposed to mitigate the negative effect induced by SLS. In summary, although usually used as a dissolution enhancer, SLS can surprisingly reduce drug dissolution by forming a poorly soluble lauryl sulfate salt. To understand this phenomenon, we systematically investigated its mechanism, prevalence, and formation rules, and demonstrate formulation strategies to mitigate the precipitation. This work provides a solid foundation for the appropriate use of SLS in pharmaceutical formulations.