One of the biggest issues facing drug formulators is the need to improve the solubility and bioavailability of active pharmaceutical ingredients (APIs). With nearly 70% of new drug candidates beset by poor water solubility and therefore poor bioavailability1, effective and scalable ways to make them more soluble are essential.
Spray drying is one of the most effective methods available to formulators. While the technique is not new – it dates back to the 1860s2 – significant technology advances in recent years have made it a go-to choice for formulating poorly soluble drugs.
Spray drying involves first dissolving the poorly soluble API, which is usually in a crystalline form, in a suitable solvent, along with any additional ingredients that might be required for the formulation. This solution is then sprayed into a hot stream of gas, creating a dry powder as the solvent evaporates. Importantly, the technique gives an immense level of control over the properties of the particles that it makes.
At its core, spray drying enables formulators to stabilize sensitive molecules, enhance solubility, and tailor the precise characteristics of the powder to suit a range of different delivery methods. It can be used on a small scale in the development lab, and the process can also be scaled up to the volumes required for commercial production.
One of spray drying’s major advantages is its ability to produce amorphous solid dispersions. These are forms of a drug where the molecules are ‘locked’ in a high-energy, non-crystalline state, allowing them to dissolve more readily in the body. If the API is spray dried alongside polymers that prevent it from turning back into crystals, this improved solubility will be retained throughout the drug’s shelf life. It is therefore a highly effective strategy for increasing bioavailability. This is important – without adequate bioavailability, the drug will not be as effective as it should be.
But improved solubility isn’t the only advantage. Other additives can also be incorporated to further improve performance. These includes carriers like cyclodextrins or silica, or ingredients designed to enhance the drug’s properties in some way.
While freeze drying has long been the go-to technique for stabilizing sensitive biologics like proteins, peptides and vaccines, it’s not without its drawbacks. It’s energy intensive, time consuming, and can often lead to formulations that are difficult to handle. Spray drying presents a compelling alternative, with milder thermal conditions and significantly faster processing times. The result will often be a powder that is easier to handle, dose, and store.
The key to the success of spray drying biologics is the rapid evaporation of the solvent. This means the delicate molecules are not exposed to heat for protracted periods of time, protecting them from degradation. Importantly, the powders will have good flowability properties, which is essential for manufacturing efficiency.
Particle engineering is a particular superpower of spray drying. By adjusting parameters like temperature, feed rate and nozzle design, scientists can precisely control particle size, density, and surface morphology. This customization allows optimized powders to be manufactured that meet specific formulation goals. It’s particularly important when creating powders for delivery to the lungs via inhalation, but equally it can be used to improve properties such as flowability for making tablets.
At Siegfried, we are integrating risk assessments, experimental design strategies, and advanced modelling tools into our spray drying workflows. It allows us to design and develop robust, scalable processes that supports everything from preclinical trials all the way through to commercial production.
With our extensive development and process expertise, we help our customers to accelerate development and to maximize operational efficiency. By taking a science- and risk-based approach, we can fine-tune product characteristics, reduce time to market, and be confident that the products we make will meet regulatory expectations.
References:
1. Bhalani, D. V., Nutan, B., Kumar, A., & Singh Chandel, A. K. (2022, August 23). Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics. Biomedicines, 10(9), 2055. https://pmc.ncbi.nlm.nih.gov/articles/PMC9495787/
2. Cal, K., & Sollohub, K. (2010). Spray drying technique. I: Hardware and process parameters. Journal of Pharmaceutical Sciences, 99(2), 575-586. https://www.sciencedirect.com/science/article/abs/pii/S0022354916303926