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.

Liquid Lipids Act as Polymorphic Modifiers of Tristearin-Based Formulations Produced by Melting Technologies

“…Poly(vinyl alcohol) (PVA) stabilized the α-form of tristearin nanoparticles for at least 9 months at refrigerator temperature [ 27 ]. The stabilization of the α-polymorph of tristearin nanoparticles achieved by PVA was greater than that of other amphiphilic molecules (sodium glycocholate and sodium glycocholate/phospholipid mixture), although the transition into the stable β-polymorph was not completely prevented [ 28 ].…”

Selenated and Sulfurated Analogues of Triacyl Glycerols: Selective Synthesis and Structural Characterization

“…High resolution mass spectra (HRMS) were recorded by Electrospray Ionization (Supporting Information). 1 Ha nd 13 CNMR spectra were recorded in CDCl 3 using Varian Mercury 400, Bruker 400 Ultrashield, and Varian Gemini 200 spectrometers operating at 400 MHz and 200 MHz (for 1 H), 100 MHz and 50 MHz (for 13 C). 77 Se NMR spectra were recorded using aB ruker 400 Ultrashield spectrometer,o perating at 76 MHz.…”

“…Acyl glycerol derivativesr epresent al arge group of molecules, finding wide application in differentf ields, as pharmaceutical, food, cosmetic, and materials ciences. [1] Suitable substituted acyl glycerols are reported to play important physiological roles in the nervouss ystem [2] and it is established that acyl glycerols from common oils show antitumora ctivity and various inhibitory actions. [3] Furthermore, acyl glycerols andt heir sulfur-and nitrogen-containing analoguesare used for the preventiona nd the treatment of neurodegeneratived iseases.…”

Kinetic Study on Alpha-Form Crystallization of Mixed-Acid Triacylglycerols POP, PPO, and Their Mixture

“…In particular, the controlled preparation of TAG crystalline particles of the metastable α polymorph is highly effective for the delivery of active drug substances. Therefore, the crystallization and stabilization of the α form in TAG nanoparticles are very important [10][11][12]. In contrast, TAG crystals in emulsion systems, such as butter, margarine, and fat spread, should be in the β form, as the crystal morphology of β can facilitate the formation of fine crystal networks [13][14][15][16].…”