Understanding Crystallisation and Why It Matters

Crystallisation is the conversion of molecules in a liquid state to a solid-state through the build-up of regular lattice structures.


As summer approaches and we start to crave ice cream more than usual, some of us may need to stock up on paracetamol to bear with the summer heat. So, what does your enthusiasm for ice cream and the headache relief brought by paracetamol have in common? Well, crystals! 

The application of crystallisation forms the bedrock of many of the pharmaceutical products necessary to everyday life. Statistics show that 80% of the world’s active pharmaceutical ingredients (API) are produced via at least one crystallisation step. API manufacturers worldwide consider crystallisation a critical separation and purification technique. Despite playing such an intricate role in the pharmaceutical manufacturing environment, pharmaceutical crystallisation requires some manufacturing practices of its own. The two significant steps involved here are nucleation and crystal growth.   Science defines crystallisation as,

".....process of formation of solid crystals from solution, melt, or by deposition directly from a gas phase."


Crystallisation is the conversion of molecules in a liquid state to a solid-state through the build-up of regular lattice structures. The intermediate phase between both states consists of manipulating molecules together into clusters of nuclei in a controlled and stable manner. As more clusters converge, they reach critical crystal size, and the nucleation phase gives way to the crystal growth phase.  

The crystal growth phase appears to be quite straightforward. Generally, as more nuclei achieve critical crystal size, an increasing trend in crystal growth is expected until maximum crystal growth is achieved. But in reality, many factors challenge this process. API crystal properties such as size, purity, shape, and molecular structure - are dictated by manufacturing process inputs and controls during the nucleation and crystal growth phases.

Crystals of chemical compound. Crystallisation is a pivotal step in Medicine API manufacturing

The end-goal is to achieve structural homogeny, that is, to achieve a uniform crystalline structure shared by all crystals. The variations in crystal structures are called polymorphs. Each polymorph possesses different physical properties that affect the end-product, such as melting point, dissolution rate, and shape. The dissolution rate in pharmaceuticals is particularly vital to cure your heat-induced headache. Because, this factor determines the rate at which paracetamol will dissolve in your body - helping you get rid of that headache!

Controlled polymorphism in pharmaceutical manufacturing is essential, and one method to achieve control is via temperature in the crystallisation process. Even the crystallisation in your ice cream recipe was tightly controlled to ensure the pleasant taste and texture you expect. 

This summer, whether you’re lucky to enjoy an ice cream in the sun, or unfortunate enough to battle a heat-induced headache, consider the crystal-connection your ice-cream shares with paracetamol. For more thought-provoking updates about crystallisation, follow Innopharma Technology for more exciting R&D information in this space. 

Chris O’Callaghan

Chris O’Callaghan is Head of Engineering within Innopharma Technology and is responsible for process analytical technologies and control products, applications development, and customer project delivery. He and his team manage the custom engineering projects required to successfully interface control systems with new and existing product lines in the continuous and batch manufacturing spaces, as well as control strategy development and deployment.

Caroline McCormack

Caroline McCormack is a Process Scientist working at Innopharma Technology and supports a number of ongoing R&D projects. She is responsible for experimentation around our process analytical technologies and advanced process control techniques currently in development, across the batch and continuous oral solid dose manufacturing space.

Horizon 2020

Innopharma Technology received up to €1.61m in research & innovation funding from EU Horizon 2020. We are developing a new product offering on Advanced Manufacturing Intelligence for crystallisation of APIs.

PIA Proud Sponsor 2020