Comparison of particle size methodology and assessment of nanoparticle tracking analysis (NTA) as a tool for live monitoring of crystallisation pathways

Abstract

Sample complexity and polydispersity presents challenges surrounding particle size measurements for nanoparticles (NPs). To ensure the delivery of high quality products to the marketplace it is imperative that this task is performed with the greatest accuracy and certainty. For this reason, particle sizing via more than one technique is critical to the success of the formulation process. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) are techniques that size particles based on their Brownian motion in liquid medium. However, each technique has advantages and disadvantages associated with its application. This study was designed with the intent of comparing these techniques in a critical manner. NPs were formed using three Biopharmaceutics Classification System class II compounds: itraconazole, ketoconazole and posaconazole, using an anti-solvent addition, bottom up method. The impact of polyethylene glycol, polyethylene glycol methyl ether and polyethylene glycol dimethyl ether with a molecular weight 2000 Da, as stabilizers, was assessed using these two particle sizing techniques. Mie light scattering theory was successfully used to explain the relationship between material composition and particle scattering power. A change in material refractive index, associated with an amorphous to crystalline solid state transformation, was predominantly responsible for the observed change in the light scattering power of posaconazole nano-dispersions. The innovative application of NTA for the live tracking of these physical processes was explored for the first time. This novel finding can serve to deepen our understanding of the dynamic crystallisation pathway undertaken by a nanoparticle.

Systematic Evaluation of PKH Labelling on Extracellular Vesicle Size by Nanoparticle Tracking Analysis

“…NTA is a widely used technique in the field and is of particular interest in this study since it is quick to perform and it provides a detailed analysis of the measuring sample leading to statistically significant nanoparticles' size distribution. Furthermore, NTA does not require processing procedures such as drying and coating which can affect the nanoparticles properties [43][44][45][46] . Hence, the present study set out with the aim of assessing the impact of PKH labelling on the size of EVs using NTA.…”

In Vivo Biocompatible Self-Assembled Nanogel Based on Hyaluronic Acid for Aqueous Solubility and Stability Enhancement of Asiatic Acid

“…The presence of a few large particles could interfere with the diameter size detection due to their contribution to a more scattered signal, resulting in overestimation of the size. Close agreement of size based on NTA and DLS can be achieved in monodispersed particles [ 55 , 56 ]. However, TEM data supported the size range observed in both DLS and NTA.…”

Nanoparticles Size Distribution Assessment During Early Synthesis Stages

“…The sample is maintained in a liquid state, so the media is similar to the biological structures from the skin. In this technique, after the determination of diffusion coefficient, each individual nanoparticle dimension is determined using the Stokes-Einstein equation [12,17], described in many literature studies: (7), where d is the hydrodynamic diameter, k is the Boltzmann constant, T is the temperature, D is represented by the diffusion coefficient and ղ is the viscosity of the medium used [12]. The properties of each medium used can influence the final results.…”

“…Even if classical techniques are also based on this equation, sample preparation and problems in multimodal dispersions analysis are disadvantages which could be overcome by DPT technique. The Stokes-Einstein equation allows the determination also of nanoparticles concentration [17], so a mathematical simulation in this case will considerably reduce the losses and the inconvenient which could appear in the experimental setups.…”