title: Industrial concentrates of dermal hesperidin smartCrystals®--production, characterization & long-term stability.
abstract: Industrial concentrates of hesperidin nanocrystals (5.0% nominal concentration) were produced applying the smartCrystal(®) combination technology of wet bead milling and subsequent high pressure homogenization. Stabilization was performed by Kolliphor(®) P 188, preservation by Euxyl PE 9010 and glycerol. Physical and chemical stability were monitored over 1.5 years of storage at 4-6 °C. The size of the bulk population stayed unchanged with about 250 nm (photon correlation spectroscopy). Absence of crystal growth by Ostwald ripening and absence of agglomerates were shown by laser diffraction (LD) and light microscopy. The LD diameter 90% was still 0.7 μm after 1.5 years. Despite the large surface of the nanosuspension in contact with the water phase, the chemical content proved also stable, only a reduction by 0.15% from 5.70% to 5.55% content was observed. The nanocrystals kept their crystalline state unchanged as shown by X-ray diffraction. The saturation solubility of the nanosuspension was more than triple compared to the raw drug powder in water. The data show the availability of a stable hesperidin concentrate as intermediate for industry to produce dermal formulations.
authors.affiliation: Pharmaceutics, Pharmaceutical Nanotechnology & NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany. Electronic address: gregoribahuromero@hotmail.com.
authors.forename: Gregori B
authors.initials: GB
authors.lastname: Romero
authors.affiliation: Pharmaceutics, Pharmaceutical Nanotechnology & NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
authors.forename: Run
authors.initials: R
authors.lastname: Chen
authors.affiliation: Applied Pharmacy, University of Applied Sciences Kaiserslautern, Campus Pirmasens, Carl-Schurz-Str. 10-16, 66953 Pirmasens, Germany.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Keck
authors.affiliation: Pharmaceutics, Pharmaceutical Nanotechnology & NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany. Electronic address: nanoteam@gmx.com.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000279:Administration, Cutaneous; D016503:Drug Delivery Systems; D004355:Drug Stability; D006569:Hesperidin / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D012995:Solubility
chemical_list: D006569:Hesperidin
keywords: Dermal application; Industrial concentrates; Nanocrystals; Nanosuspensions; Nanotechnology; Stability