The Role of Particle Morphology in the Pharmaceutical Industry

There are several particle characteristics that are of critical importance when considering pharmaceutical properties. One of these is particle size (granulometry), and the other, perhaps less immediately obvious, is the morphology – the particle’s shape.

When it comes to all technical properties by which powders are measured (bulk density, flowability, surface areas etc.), the combination of granulometry and morphology are the key determinants that a chemist needs to consider when developing a product.

Understanding the role of particle morphology

The role of particle morphology for any given application will vary significantly. For example, if the purpose of the powder was to create high flowability or be in an optimal condition for particle melting and spraying, researchers will want to establish spherical particle shapes. On the other hand, if the goal is to create something abrasive, particles need to have high angularity in shape.

Pharmaceutical powder technology is extremely complex because the preparation, creation, and managing of the process has to be precise and create accurate results. The technology used needs to be able to deal with examining all the materials, formulations, additives, and processes. This ensures consistency and delivers exact results in the properties and performance of the particles.

Benefits of powdered drugs

One advantage of powdered drugs is that they can be delivered directly to the lungs (using an inhaler). This, of course, has been the traditional approach for asthma patients and other patients in need of pulmonary drugs. However, there’s a growing awareness that inhalation can be the preferable option because it offers such a rapid onset of action.

Indeed, the pulmonary option is commonly seen as a more convenient and less intrusive alternative. It’s the same for doctors and medical facilities because there is a reduced need to supervise drug delivery and no need to sterilise drug delivery products (reducing costs). It’s also worth noting that pulmonary administration means smaller doses in each intake and the potential side effects could be minimised.

The challenges of powdered drugs

One challenge that researchers and manufacturers face when working with powders is that they often fail to discharge reliably from bins, hoppers or silos. Powders also often have poor quality or unreliable flow in feeders and dosing machines. This means the manufacturing process can be regularly interrupted to the point of complete shutdowns in order to correct flow restrictions and stoppages.

When researching drugs for pulmonary droplet delivery, particle size and shape are critical. Particles that arelarger than five microns will not go deep into the lungs, and those that are too small – smaller than one micron – may be exhaled. Additionally, as we’ve discussed above, the efficiency in which a particle can be absorbed relies heavily on its morphology.

Popular methods of reducing particle size

Micronization

The most common process for reducing size is simple and well established – micronization. Micronization makes use of jet mills, does not use solvents, and can be used for thermally sensitive materials.

Solution or spray drying

Particles with amorphous regions that might crystallise over time or particles that are difficult to disperse over time because of electrostatic charges are a few examples of when micronization would not be effective. Alternative processes might include engineering particles by drying them from a solution or spray drying. This is an effective way of creating particles of a specific density and size.

Wet-polishing

Wet-polishing combines size-reduction technologies with isolation approaches and co-crystallisation is used to create particles of whatever required size while also incorporating excipients.

Other methods also include supercritical-fluid (SCF) antisolvent processing and co-crystallisation (a more novel process).

Particle imaging technology is providing the most accurate measurements

TheMalvern Morphologi 4 is an example of technology custom designed to accurately and measure the characteristics of particles. As a fully automated way to measure particle size, shape, count and its application for pulmonary administration, this device is an ideal way to develop a full understanding of the characteristics of a particle.

This technology is able to measure particle sizes from 0.5µm to >1300µm, and size parameters including circle equivalent diameter, length, width, perimeter, area, max distance, sphere equivalent vol, fibre total length and fibre width. The Malvern Morphologi 4 has a wide range of applicationssuch as automation of manual microscopy methods and the ability to detect foreign particulates in pharmaceutical dry powders, liquids and creams.

The Morphologi 4-ID adds further capabilities by delivering Morphologically-Directed Raman Spectroscopy (MDRS). The MDRS technique integrates the static imaging capabilities of the Morphologi 4 with Raman spectroscopy to enable the component-specific morphological characterisation of different chemical species in a mixture. Chemical identification of specific particles within a multi-component mixture can be useful particularly for identifying contaminants and for the rapid development of generic pharmaceutical formulations.

For more information on what the Malvern Morphologi 4 and Morphologi 4-ID can do in helping to measure and refine powders, please contact us today at ATA Scientific.