title: Mixed Micelle System Produced by Interaction Between Transglycosylated Stevia and an Ionic Surfactant Improves Dissolution Profile of Mefenamic Acid.
abstract: Transglycosylated stevia (stevia-G) can effectively improve the dissolution and bioavailability of poorly water-soluble drugs. Furthermore, addition of an ionic surfactant to stevia-G solution has been shown to enhance the dissolution effect of stevia-G on flurbiprofen. Herein, 4 surfactants, namely sodium dodecyl sulfate, sodium N-dodecanoylsarcosinate, sodium monododecyl phosphate, and lauryltrimethylammonium chloride (LTAC) were screened to investigate their synergistic effect with stevia-G in enhancing the solubility of mefenamic acid (MFA). The ternary formulation containing LTAC produced the highest increase in solubility, whereas the binary MFA/LTAC formulation did not increase the solubility of MFA. Surface tension was evaluated to analyze the interaction between stevia-G and each ionic surfactant, wherein the Rubingh model was applied to predict mixed micelle formation between stevia-G and LTAC. Interaction parameters calculated by the Rubingh model reflected mixed micelle formation between stevia-G and LTAC relative to the self-interactions of the 2 individual surfactants. All interaction parameters in this system showed negative values, indicating a favorable interaction (e.g., hydrogen bond or electrostatic and dipole) between binary components in the mixed micelles. Spray-dried particles of ternary formulations (MFA/stevia-G/LTAC) were prepared to evaluate the dissolution profile and physicochemical properties. Dissolution profiling showed that the concentration of MFA released from spray-dried particles was significantly higher than untreated MFA.
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fujimori
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: ytozuka@gly.oups.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
mesh_terms: D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006031:Glycosylation; D008528:Mefenamic Acid / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D012995:Solubility; D036625:Stevia / Q000737:chemistry / Q000378:metabolism*; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D008823:Micelles; D013501:Surface-Active Agents; D008528:Mefenamic Acid
keywords: Rubingh model; ionic surfactants; mefenamic acid; mixed micelles; transglycosylated stevia