title: Stability of the Metastable α-Polymorph in Solid Triglyceride Drug-Carrier Nanoparticles.
abstract: Colloidal dispersions of crystalline nonpolar lipids are under intensive investigation as carrier systems in pharmaceutics and nutrition. In this context, the controlled preparation of particles in a metastable polymorphic state is of some interest for the delivery of active substances. In the present study, tristearin particles stabilized with three α-polymorph-preserving emulsifier regimes ((I) sodium glycocholate/saturated long-chain phospholipids, (II) sodium glycocholate, and (III) poly(vinyl alcohol) (PVA)) were investigated concerning the stability of the metastable α-polymorph after controlled crystallization of the particles from the melt. Upon long-term storage, the α-polymorph was preserved best in PVA-stabilized dispersions, followed by those stabilized with the glycocholate/phospholipid mixture and finally those stabilized solely with the bile salt. In particular for rapidly crystallized nanoparticles, the formation of an α-polymorph with highly reduced lamellarity was observed. According to time-/temperature-resolved synchrotron X-ray diffraction analysis with simultaneous DSC (differential scanning calorimetry) studies, this less-ordered α-polymorph transformed into the common, lamellar α-form upon heating. Although the presence of the less-ordered form is probably related to the extraordinarily high stability of the metastable α-polymorph observed in some of the dispersions, it could not completely prevent the transition into the stable β-polymorph. The higher the transition temperature of the less-ordered α-form to the ordered one, the slower was the polymorphic transition to the stable β-polymorph. To estimate the polymorphic stability of the differently stabilized particles upon isothermal long-term storage, standard DSC measurements on samples stored at 23 °C for 4 weeks seem to be of predictive value.
authors.affiliation: †Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstr. 1, D-38106 Braunschweig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Joseph
authors.affiliation: §Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 6/IV, 8010 Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Rappolt
authors.affiliation: ∥Institut für Chemische und Thermische Verfahrenstechnik, Technische Universität Braunschweig, Langer Kamp 7, D-38106 Braunschweig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schoenitz
authors.affiliation: ∥Institut für Chemische und Thermische Verfahrenstechnik, Technische Universität Braunschweig, Langer Kamp 7, D-38106 Braunschweig, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Huzhalska
authors.affiliation: ∥Institut für Chemische und Thermische Verfahrenstechnik, Technische Universität Braunschweig, Langer Kamp 7, D-38106 Braunschweig, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Augustin
authors.affiliation: ∥Institut für Chemische und Thermische Verfahrenstechnik, Technische Universität Braunschweig, Langer Kamp 7, D-38106 Braunschweig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Scholl
authors.affiliation: †Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstr. 1, D-38106 Braunschweig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bunjes
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D006000:Glycocholic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D014280:Triglycerides; D011142:Polyvinyl Alcohol; D006000:Glycocholic Acid