Component-specific Particle Size

Follow that particle!

I’ve always thought it would be great to be the innocent driver in a movie chase scene who has to respond to the hero’s demand to ‘Follow that car’ as they try to keep tabs on the villain. I always imaged that this would unlock the silent racing driver within me, giving me the excuse to forget about speed limits and drive at the limits of my car’s performance. I’d also get the chance to practice my handbrake turns!

Although I have never been engaged in a car chase, nor am I ever likely to be, there is one demand that I have helped Malvern’s customers in achieving, and that is to ‘follow that particle!’. For most of my time at Malvern, I have been involved in the application of laser diffraction. This is a great technique for obtaining general particle size information. However, it assumes that all the particles in a sample are made of the same material, so the chase is lost from the outset! This is where the Morphologi G3-ID has come in to help me and my colleagues to be the ‘heroes’ of the particle chase. By applying Morphologically-Directed Raman Spectroscopy (MDRS), researchers are able to obtain component-specific particle size distributions from samples containing different particle types. So, it is now possible to ‘follow that particle’ or, at the very least, to follow what is happening to a group of particles which have a similar composition.

“So what?”, I hear you ask. In my long wished-for movie car chase, the end point is the capture of the villain. What does applying MDRS achieve?

One area where MDRS is making a significant contribution is in understanding the impact of processing conditions on the properties of pharmaceutical oral solid dose drug products. One of the Critical Material Attributes associated with these products is the particle size of the active pharmaceutical ingredient (API) contained within the formulation. Particle size defines the dissolution rate of the API, which in turn relates to its bioavailability. API particle size must be controlled to ensure the drug reaches the concentration required to provide a therapeutic effect within the patient (a concentration referred to as the ‘therapeutic window’). If the concentration is too low, the patient gains no benefit from taking the drug product. If the concentration is too high, it may risk patient safety.

API particle size is normally controlled prior to blending with the excipients required to create the final dosage form. However, what is poorly understood is how blending and pneumatic transport of the formulation affects particle size. In order to understand this better, researchers at BMS in the UK applied MDRS to measure powder blends at different points throughout an oral solid dose manufacturing process. The technique enabled them to follow the API particles, and confirmed that processing caused a reduction in the API particle size. The degree of particle attrition observed was related to the mechanical properties of the excipient used in the formulation, as well as to the energy input associated with each processing stop.

John Gamble, the lead researcher engaged in this study at BMS, will be presenting his work in a Malvern webinar this month. Find out more about how MDRS is applied? Who knows, maybe you’ll then be able to understand the (scientific) excitement of being able to ‘follow that particle!’.