title: Fluorescence investigation of a specific structure formed by aggregation of transglycosylated stevias: solubilizing effect of poorly water-soluble drugs.
abstract: Spray-dried particles (SDPs) with indomethacin (IND) and alpha-glycosyl transferase-treated stevia (Stevia-G) indicated extremely high dissolution rates and apparent solubility compared to particles of a ground mixture and a physical mixture of IND/Stevia-G. The apparent solubility of IND from SDPs was 5-fold higher than that of untreated IND. We investigated the solubility-enhancing effect of Stevia-G towards hydrophobic materials by using fluorescence spectroscopy. 1-Naphthoic acid (1-NPA) and pyrene were used as hydrophobic fluorescence probes. Although both the ground mixture and SDPs of 1-NPA/Stevia-G exhibited halo patterns in powder X-ray diffraction, the fluorescence spectra of 1-NPA solely in SDPs indicated a monomolecularly dispersed state of 1-NPA. The plot of the pyrene I(1)/I(3) ratio versus the Stevia-G concentration showed a sigmoidal curve as a function of the Stevia-G concentration, suggesting the existence of a hydrophobic environment around pyrene molecules under high Stevia-G concentrations. The critical micelle concentration calculated from the pyrene I(1)/I(3) plot was about 16mg/mL. Based on results from the static quenching plots, the micellar aggregation number of Stevia-G was estimated as ca.15. Therefore, the hydrophobic steviol-skeleton of Stevia-G made a hydrophobic core around a hydrophobic molecule. This specific structure formed by Stevia-G molecules led to an enhancement of the apparent solubility of poorly water-soluble drugs.
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Fusatoshi
authors.initials: F
authors.lastname: Asamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006031:Glycosylation; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations; D011208:Powders / Q000737:chemistry; D011721:Pyrenes / Q000737:chemistry; D012995:Solubility; D013050:Spectrometry, Fluorescence / Q000379:methods*; D036625:Stevia / Q000737:chemistry*; D013499:Surface Properties; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D002264:Carboxylic Acids; D004337:Drug Carriers; D008823:Micelles; D009281:Naphthalenes; D004364:Pharmaceutical Preparations; D011208:Powders; D011721:Pyrenes; D014867:Water; C085312:1-naphthoic acid; C030984:pyrene; D007213:Indomethacin