# Understanding Nanoparticle Performance Through Surface Analysis

By AZoNano.com Staff Writers

## Introduction

The nature and the extent of nanoparticle surfaces is a very important element of particulate dispersion formulation. For instance, the wetted surface area determines the quantity of surfactant required to ensure complete particle coverage and accordingly, optimal particle dispersion.

Irrespective of the industry in which you work, optimizing product performance and ensuring end product quality require control of the particle-liquid interface. Until now, direct measurements of wetted particle surfaces were not possible.

Particles were initially separated from the liquid in which they were created or used and then BET gas absorption measured the same. Unfortunately, gas adsorption on a dried particle surface has little relevance to the behavior or those particles in liquids.

It was also a challenging process to separate particles from the formulation in which they are dispersed, often particles aggregate on drying. This tedious and complex sample preparation and measurement process limited the use of surface area measurements in dispersion formulation development.

Measurements of particle distribution and size are very rapid and offer some information, but have several limitations:

• They are confined to very dilute systems
• They assume that the particles are spherical
• They aren’t very sensitive to measuring small particles amongst large ones
• They provide no information about the particle surface chemistry

## Calculations

The following formula is used to calculate particle surface area from the dispersion relaxation time:

Rav = ψpS L ρp (Rs-Rb) + Rb

where:

• Rd= Dispersion relaxation rate= 1/Td

• ψp = Particle/liquid volume ratio

• S = Surface area [m2/gram]

• L = Surface liquid layer thickness [m]

• ρb = Particle density

• Rs= Relaxation rate surface liquid = 1/Ts

• Rb= Relaxation rate bulk liquid = 1/Tb

This formula can be reduced by defining a constant, Ka, using a standard reference material:

Ka = L ρb (Rs – Rb)

where:

• Rsp = Rd/Rb - 1

• Rd = Ka S ψp + Rb

• S= RspRb/ Kaψp

Most real particles are not spherical, most real particles are not monodisperse, and surface chemistry can have a significant impact on dispersion performance.

A novel approach to quantifying the nature and extent of nanoparticle surfaces using NMR is available that could be an invaluable tool to scientists working in product development, process development, or quality.

The Acorn Area’s patented approach to quantifying the wetted surface of nanoparticles does not need any sample preparation and takes less than 5 minutes to measure dispersion behavior.

## The Acorn Area

The Acorn Area makes use of nuclear magnetic resonance (NMR) to measure wetted nanoparticle surfaces. It is based on the observation that liquid close to the particle surface has a relaxation timeT2s orders of magnitude shorter than the relaxation T2bulk of liquid far away from the particle surface.

Liquid molecules exchange between the surface of the particle and the bulk liquid rapidly. While measuring the relaxation time of a particle dispersion, an average relaxation time is observed that is a weighted average of the volume of liquid on the particle surface and the volume of liquid far away from the particle surface.

Figure 1. Relaxation Time and Rate versus weight % 100 nm TiO2

This approach has a number of advantages. It works well for concentrated systems. In fact, the higher the particle concentration, the greater the volume of surface associated liquid and larger the relaxation time shift in comparison with the pure liquid.

Time is the second advantage. Relaxation measurements require less than 2 minutes for completion.

Figure 2. Particle Surface Area and Size as a function of Milling Time

These data compare wetted surface area via NMR with particle size measurements via laser diffraction as a function of milling time. Even though the size measurements may plateau after a milling time of 30 minutes, surface area measurements confirm the continuous reduction in particle size as a function of milling time for this pharmaceutical API.

## Conclusion

It is important to note that the presence of API fines in a drug product can significantly alter the pharmacokinetics of drug absorption and in some cases, result in cytotoxicity. Furthermore the presence of fines can cause issues with the physical stability of the drug product.

The surfactant loading required to stabilize a colloidal dispersion is directly related to the wetted surface of the particle, hence direct measurement of the wetted surface area is critical to formulation development.

XiGo Nanotools was founded by Sean Race and Dr. David Fairhurst in 2005 with the mission to provide new innovate “tools” for the emerging nanomaterials industry.

The Acorn Area is designed to measure the wetted surface area of concentrated dispersions with little or no sample preparation, providing a viable complementary technique to BET surface area, analyzing nanoparticles as they are made or used, dispersed in liquids.

Our goal is to provide scientists, researchers, and corporations with tools that are easy to use and serve as wide and diverse a customer base as possible. We have incorporated the latest technology available into an integrated, high quality package that provides precise measurements in a very small footprint.

This information has been sourced, reviewed and adapted from materials provided by XiGo Nanotools.