title: Solubilization of active ingredients of different polarity in Pluronic® micellar solutions - Correlations between solubilizate polarity and solubilization site.
abstract: The solubilization of two pharmaceutically active ingredients (AI) with significantly different water solubility, namely carbamazepine and fenofibrate (solubility of 150ppm and 10ppm, respectively), has been investigated using a series of Pluronics® (Poloxamers) containing different ethylene oxide and propylene oxide (EO/PO) units in the molecule. The results show largely enhanced solubilization of fenofibrate by Pluronic® micelles that increases with the PPO chain length provided the temperature is above the critical micelle temperature (cmt). In contrast the more water-soluble carbamazepine only shows a moderate increase in solubilization upon addition of Pluronics®. Small angle neutron scattering (SANS) and pulsed field gradient (PFG) NMR experiments show that the solubilization of fenofibrate occurs in the core of the micelles, whereas carbamazepine shows no direct association with the micelles. These clearly different solubilization mechanisms for the two AIs were confirmed by Nuclear Overhauser Enhancement Spectroscopy (NOESY) experiments, which show that fenofibrate interacts only with the PPO core of the micelle, whereas carbamazepine interacts with both PPO and PEO similarly. Accordingly, the large enhancement of the solubilization of fenofibrate is related to the fact that it is solubilized within the PPO core of the Pluronic® micelles, while the much more moderate increase of carbamazepine solubility is attributed to the change of solvent quality due to the presence of the amphiphilic copolymer and the interaction with the EO and PO units in solution.
authors.affiliation: Stranski-Laboratorium für Physikalische und Theoretische Chemie, Institut für Chemie, Straße des 17. Juni 124, Sekr. TC7, Technische Universität Berlin, D-10623 Berlin, Germany; BASF SE, Carl-Bosch-Straße 38, D-67056 Ludwigshafen am Rhein, Germany.
authors.forename: Viet
authors.initials: V
authors.lastname: Nguyen-Kim
authors.affiliation: Stranski-Laboratorium für Physikalische und Theoretische Chemie, Institut für Chemie, Straße des 17. Juni 124, Sekr. TC7, Technische Universität Berlin, D-10623 Berlin, Germany; Helmholtz-Zentrum-Berlin, Lise-Meitner-Campus, Hahn Meitner Platz 1, 14109 Berlin, Germany.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Prévost
authors.affiliation: BASF SE, Carl-Bosch-Straße 38, D-67056 Ludwigshafen am Rhein, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Seidel
authors.affiliation: BASF SE, Carl-Bosch-Straße 38, D-67056 Ludwigshafen am Rhein, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Maier
authors.affiliation: BASF SE, Carl-Bosch-Straße 38, D-67056 Ludwigshafen am Rhein, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Marguerre
authors.affiliation: BASF SE, Carl-Bosch-Straße 38, D-67056 Ludwigshafen am Rhein, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Oetter
authors.affiliation: 89 Nash Grove Lane, Wokingham, Bershire, UK.
authors.forename: Tharwat
authors.initials: T
authors.lastname: Tadros
authors.affiliation: Stranski-Laboratorium für Physikalische und Theoretische Chemie, Institut für Chemie, Straße des 17. Juni 124, Sekr. TC7, Technische Universität Berlin, D-10623 Berlin, Germany. Electronic address: michael.gradzielski@tu-berlin.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Gradzielski
mesh_terms: D002220:Carbamazepine / Q000737:chemistry*; D011345:Fenofibrate / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D020442:Poloxamer / Q000737:chemistry*; D012995:Solubility; D012996:Solutions
chemical_list: D008823:Micelles; D012996:Solutions; D020442:Poloxamer; D002220:Carbamazepine; D011345:Fenofibrate
keywords: Carbamazepine; Fenofibrate; Pluronics®; Solubilization enhancement; Solubilization mechanisms