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Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate.
J Pharm Sci. 2019 Jan; 108(1):516-524.JP

Abstract

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, [RTV2+][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 [RTV2+][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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Guo Y
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, S.E. Minneapolis, Minnesota 55455.
Wang C
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, S.E. Minneapolis, Minnesota 55455.
Dun J
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, S.E. Minneapolis, Minnesota 55455.
Du L
Material & Analytical Sciences, Boehringer Ingelheim, Ridgefield, Connecticut 06877.
Hawley M
Material & Analytical Sciences, Boehringer Ingelheim, Ridgefield, Connecticut 06877.
Sun CC
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, S.E. Minneapolis, Minnesota 55455. Electronic address: sunx0053@umn.edu.

MeSH

Chemistry, PharmaceuticalHydrogen-Ion ConcentrationMicellesRitonavirSodium Dodecyl SulfateSolubilitySurface-Active AgentsTabletsWettability

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30389564

Citation

Guo, Yiwang, et al. "Mechanism for the Reduced Dissolution of Ritonavir Tablets By Sodium Lauryl Sulfate." Journal of Pharmaceutical Sciences, vol. 108, no. 1, 2019, pp. 516-524.
Guo Y, Wang C, Dun J, et al. Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate. J Pharm Sci. 2019;108(1):516-524.
Guo, Y., Wang, C., Dun, J., Du, L., Hawley, M., & Sun, C. C. (2019). Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate. Journal of Pharmaceutical Sciences, 108(1), 516-524. https://doi.org/10.1016/j.xphs.2018.10.047
Guo Y, et al. Mechanism for the Reduced Dissolution of Ritonavir Tablets By Sodium Lauryl Sulfate. J Pharm Sci. 2019;108(1):516-524. PubMed PMID: 30389564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate. AU - Guo,Yiwang, AU - Wang,Chenguang, AU - Dun,Jiangnan, AU - Du,Liying, AU - Hawley,Michael, AU - Sun,Changquan Calvin, Y1 - 2018/10/30/ PY - 2018/08/22/received PY - 2018/09/28/revised PY - 2018/10/22/accepted PY - 2018/11/6/pubmed PY - 2020/2/18/medline PY - 2018/11/4/entrez KW - dissolution KW - pH KW - precipitation KW - ritonavir KW - salt KW - sodium lauryl sulfate SP - 516 EP - 524 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 108 IS - 1 N2 - 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, [RTV2+][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 [RTV2+][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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/30389564/Mechanism_for_the_Reduced_Dissolution_of_Ritonavir_Tablets_by_Sodium_Lauryl_Sulfate_ DB - PRIME DP - Unbound Medicine ER -