title: Wetting effects versus ion pairs diffusivity: interactions of anionic surfactants with highly soluble cationic drugs and its impact on tablet dissolution.
abstract: A study was conducted to develop a mechanistic understanding of dissolution of a highly soluble cationic drug, metformin hydrochloride, under the influence of anionic surfactants, sodium alkyl sulfates. The surfactants did not influence the saturated solubility of the drug, but reduced the surface tension of the dissolution media as the alkyl chain length increased. Their influence on tablet wetting based on the contact angles did not show any trend. The dissolution of 850 mg metformin hydrochloride tablets in 0.1 N HCl and pH 4.5 acetate buffer with 0.01% (w/v) sodium n-octyl sulfate (C8), sodium n-decyl sulfate (C10), or sodium n-tetradecyl sulfate (C14) was similar to the control, but was enhanced by sodium lauryl sulfate (C12). At 0.1% (w/v) concentration, the dissolution was not enhanced by C12 because the reduction in surface tension was counterbalanced by an increase in hydrophobic ion pairs that showed slower diffusivity by nuclear magnetic resonance. At 0.1% (w/v), metformin also formed an insoluble salt (1:2 molar ratios) with C10 (pH 1.2), C12, and C14 (pH 1.2 and 4.5) but not with C8. Three competing factors influenced the drug dissolution by surfactants: reduction in surface tension of the dissolution media, ion pairs with low diffusivity, and formation of an insoluble salt.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wong
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.
authors.forename: Yande
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.|CDER, FDA, Silver Spring, Maryland.
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, Moreton, Merseyside, CH46 1QW, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Timmins
mesh_terms: D002412:Cations / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008687:Metformin / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry*; D017155:Wettability
chemical_list: D002412:Cations; D007477:Ions; D013501:Surface-Active Agents; D013607:Tablets; D012967:Sodium Dodecyl Sulfate; D008687:Metformin
keywords: NMR; critical micelle concentration; diffusion; dissolution; metformin salts; sodium alkyl sulfate; solubility; wetting