Internal Structure of Nanometer-Sized Droplets Prepared by Antisolvent Precipitation

Abstract

Antisolvent precipitation (AP) is a low-cost and less-invasive preparation alternative for organic nanoparticles compared to top-down methods such as high-pressure homogenization or milling. Here we report on particularly small organic nanoparticles (NPs) prepared by AP. It has been found for various materials that these NPs in their liquid state exhibit a significant degree of molecular order at their interface toward the dispersion medium including ubiquinones (coenzyme Q10), triglycerides (trimyristin, tripalmitin), and alkanes (tetracosane). This finding is independent of the use of a stabilizer in the formulation. While this is obviously a quite general interfacial structuring effect, the respective structural details of specific NPs systems might differ. Here, a detailed structural characterization of very small liquid coenzyme Q10 (Q10) NPs is presented as a particular example for this phenomenon. The Q10 NPs have been prepared by AP in the presence of two different stabilizers, sodium dodecyl sulfate (SDS) and pentaethylene glycol monododecyl ether (C12E5), respectively, and without any stabilizer. The NPs’ size is initially analyzed by photon correlation spectroscopy (PCS). The SDS-stabilized Q10 NPs have been studied further by differential scanning calorimetry (DSC), small-angle X-ray and neutron scattering (SAXS, SANS), wide-angle X-ray scattering (WAXS), and cryogenic transmission electron microscopy (CryoTEM). A simultaneous analysis of SAXS and contrast variation SANS studies revealed the molecular arrangement within the interface between the NPs and the dispersion medium. The Q10 NPs stabilized by SDS and C12E5, respectively, are small (down to 19.9 nm) and stable (for at least 16 months) even when no stabilizer is used. The SDS-stabilized Q10 NPs reported here, are therewith, to the best of our knowledge, the smallest organic NPs which have been reported to be prepared by AP so far. In particular, these NPs exhibit a core–shell structure consisting of an amorphous Q10 core and a surrounding shell, which is mainly composed of oriented Q10 molecules and aligned SDS molecules. This structure suggests a significant amphiphilic behavior and a rather unexpected stabilizing role of Q10 molecules.

A novel experimental approach for nanostructure analysis: simultaneous small-angle X-ray and neutron scattering

“…Thus, the SAXS technique is used to obtain comprehensive structural details. For many science cases (e.g., core-shell colloids, biological systems, nanoparticle-protein complexes), the need to combine SAXS and SANS to resolve structural information has been reported (Schindler et al, 2015, Hennig et al, 2013, Spinozzi et al, 2017, Schuldes et al, 2019. As an example, for the suspension of organic-coated solid inorganic NPs (Schindler et al, 2019, Schindler et al, 2015, Schindler et al, 2017, the SANS method is particularly sensitive to the hydrogenated organic shell while the core is transparent to neutrons.…”

“…However, X-rays interact prevalently with the electron shell of the atoms, while neutrons interact with their nuclei, and thus the two radiations offer two different contrasts (X-ray and neutron scattering cross section). The SAS method has been used with great success in investigating the structure of soft condensed matter such as emulsions (Schmiele et al, 2016), micelles (Schmutzler, Schindler, Goetz et al, 2018; Schmutzler, Schindler, Schmiele et al, 2018), liquid crystalline structures (Gehrer et al, 2014;Schmiele, Gehrer et al, 2014;Schö nhals et al, 2010) and organic nanoparticle (NP) dispersions (Schuldes et al, 2019;Schmiele, Schindler et al, 2014;Unruh, 2007). For advanced functional materials applications (e.g.…”

“…The X-ray interacts prevalently with the electron shell of the atoms, while neutrons interact with their nuclei, thus, both radiations offer two different contrasts (X-ray and neutron scattering cross-section). The SAS method has been used with great success in investigating the structure of soft condensed matter such as emulsions (Schmiele et al, 2016), micelles , Schmutzler, Schindler, Schmiele, et al, 2018, liquid crystalline structures (Gehrer et al, 2014, Schonhals et al, 2010, and organic nanoparticle (NP) dispersions (Schuldes et al, 2019, Schmiele, Schindler, et al, 2014, Unruh, 2007. For advanced functional materials (e.g., sensors, solar cells, and lithium ion batteries), SAXS and SANS are important techniques to study the formation, growth, and stabilization of inorganic nanomaterials (Schindler et al, 2015, Schindler et al, 2017, Wang et al, 2015, Wang et al, 2019, Zheng et al, 2018, Mohl et al, 2018, Futscher et al, 2019.…”

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

“…Within a collaboration between Bayer and the Erlangen cluster of Excellence "Engineering of Advanced Materials", located at the university of Erlangen (FAU), five interconnected sub-projects studied the process chain from particle formation (see Figure 6) by top-down (nanomilling in a stirred media mill [49] and bottom-up nanoparticle formation by precipitation [50]. Particle formation was coupled to post-processing by formulationsupported spray drying and tablet formation [51] and comprehensive characterization along the process chain [52]. The latter included in situ techniques by small-angle X-ray (SAXS) and neuron scattering (SANS) to resolve nanoparticle formation even at short time scales and a wide range of methods for nanoparticle material characterization all the way up from formation to dissolution studies of formulated tablets.…”

Simultaneous SAXS/SANS Method at D22 of ILL: Instrument Upgrade

“…Small angle scattering (SAS) of X-rays (SAXS) and neutrons (SANS) are non-destructive powerful techniques which have been utilized successfully for investigating nanostructured materials such as metal nanoparticles [1,2], emulsions [3], micelles [4,5], electrolytes [6,7], liquid crystals [8,9] and organic nanoparticles [10][11][12][13]. The SAS technique provides nanoscale information including shape, size, and size distribution as well as spatial distribution of dispersed materials in solution [14,15].…”