For spray dried powders, powder characterisation is a key step in the development of a formulation, process or product. Understanding the key physical characteristics can mean the difference between success and failure of a pharmaceutical product.

The following are just some important properties of powders that we routinely assess:

Particle Size

The particle size distribution in a dry powder can be critical for specific applications such as nasal or inhaled delivery. This can be measured in several different ways. For example:

• A simple sieved fractionation can be useful, although the fraction sizes can be relatively wide.
• Laser diffraction provides a higher fidelity measurement. This can be undertaken in the dry state (using a dispersant gas to ensure primary particles are measured) or in the wet state (in a suitable antisolvent for the material).

Ensuring a representative sample is used for measurement is vital, especially when broader size distributions are encountered.

Morphology / Shape

Particle morphology can be dependent upon the numerous formulation and process factors, all affecting the way droplets form and dry into particles. Particle size, density and morphology affect important powder properties such as flow and aerodynamics. Examples are:

• SEM imaging is a qualitative measure, which allows you to observe what powder has been made. Sampling is key to ensure a representative sample is imaged.
• Laser or optical techniques using single particle imaging provides a more quantitative measure; these can be used for a less subjective comparison of samples.

Density

Powder density and flow measurements are important characteristics in downstream processing, especially during automated filling. Density of particles produced may be controlled or tuned by the droplet drying process, the formulation and solvent systems used during manufacture.

Aerodynamics

Particle aerodynamics are important for product performance in inhalation delivery. The aerodynamic particle size distribution is often quite different to the geometric size distribution. Morphology and density also play a role in how well a particle may fly and be carried in to the lung or the nasal cavity. Cascade impactor testing tests the aerodynamic performance of formulations for inhaled and nasal delivery.

Thermal properties

The thermal properties of a powder should be understood, both in reaction to heat and to humidity. Considering the effects of temperature, different materials may melt or become sticky depending on whether they are crystalline or amorphous. Thermal analysis of powders by differential scanning calorimetry (DSC) and dynamic vapour sorption/desorption (DVS) will give an indication of suitable storage conditions and any packaging challenges that may need to be addressed.

• DSC can give an insight to the structure of a formulation and interactions between its components. It also indicates any potential stability issues that may arise.

The relatively large surface area of powders means that the effects of humidity can be quite marked, ranging from no impact, through stickiness and aggregation to deliquescence.

• Using DVS the effect of a wide range of relative humidities on a sample can be studied and the reversibility of any effect can give insight to its mechanism; such as absorption, adsorption or crystallisation.

Powder characterisation is vital to successful formulation and process development. It enables us to identify and control the parameters that affect the key powder characteristics. The techniques described above are the ones most routinely applied, but there are many others that can be used, depending upon the development stage, the formulation and the application.