As more new molecular entities (NMEs) are poorly soluble, a wide array of enabling formulation technologies for drug development are being evaluated. Among the emerging options are amorphous solid dispersions (ASDs), liquid dispersions, and co-precipitation. Of several marketed ASD drugs, spray drying is the most popular approach to convert crystalline drugs into amorphous powder, due, in part, to a simpler downstream process to formulate ASDs into solid oral dosage forms (SODF).
Successful spray drying takes more than equipment. Ascendia Pharmaceutical Solutions blends its expertise with modern U.S.-based facility with its BEST (Brilliant Technology, Excellent Service, Superior Quality, Trust) approach to provide excellent small-batch spray drying services. In fact, Ascendia Pharmaceutical Solutions has a proven track record in spray drying of molecules that have not traditionally been considered to be ideal candidates for the solid dispersion process.
Spray drying is a gentle one-step continuous manufacturing process that involves creating dry powder directly from a fully dispersed one-phase mixture of drug and polymer dissolved in a common solvent or slurry mixture of drug with typically high concentrations of polymer. The slurry is subjected to spray as fine droplets by atomization controlled with a stream of hot drying nitrogen gas typically conducted between 50° C - 100° C. The spray-dried powder dries rapidly, as the solvent evaporates. The product is collected in a cyclone, and the solvent is reconciled after condensing through a chiller.
A number of benefits are realized through spray drying. It allows quick and efficient transformation of liquids into powders for consistent output. Spray drying also produces particles with a specific size, morphology, and distribution, and can improve the efficacy, stability and shelf life of sensitive drugs and biologics. Highly crystalline active pharmaceutical ingredients (APIs) can be completely miscible and homogeneously distributed within polymeric carriers or matrices in the amorphous state. It is ideal for heat-sensitive biologics, like monoclonal antibodies and mRNA, because it can maintain their molecular natural structures and activities.
One aspect that should be noted is that spray drying is not a straightforward process. Spray drying factors (Figure 1) affect the drug product’s quality. So, an attentive, customized approach is necessary for effective spray drying.
A CDMO must have experience in spray drying to avoid potential pitfalls. For example, there is the possibility for degradation of heat-sensitive drugs due to high temperatures during spray drying process and/or secondary drying process. Selecting an appropriate solvent is critical, as well. A CDMO must understand this, as post-process residual solvents can easily impact the stability and safety of the final product.
Let’s discuss some of those challenges more in-depth. Spray drying requires a significantly large number of solvents, which can be an impediment in developing an amorphous drug because of incomplete drying of ASD powder. At a smaller scale, it is highly feasible to save time and cost, but for scale-up, large amounts of solvents are required, and hence poses the challenges.
Therefore, a more efficient drying process is necessary to control the residual solvents per ICH guidelines. In such cases, solvents with low boiling points and APIs with relatively higher solubility are often preferred to control particle size and produce higher ASD yield.
The drug’s stability in the solvent feed requires a longer spray drying process. It can lead to generating impurities by thermal degradation, so care must be taken to minimize the undesired side reactions and related impurities.
Ascendia Pharmaceutical Solutions has become the “go-to” CDMO for small-batch spray drying projects. Our advanced expertise and technical know how to implement processes lead to time saving and cost for effective scale-up. Proficiency in spray drying helps us recognize formulations that will have issues – such as viscosity – later in the drug development process and optimize them for success.
Our teams of scientists are proficient at conducting spray drying in aseptic environment as well. Our expertise in transitioning formulations from non-cGMP environments to cGMP environments at a small scale formulation helps create a seamless transition from Ascendia CDMO - to drug manufacturers for larger-scale production.
Ascendia Pharmaceutical Solutions’ aseptic spray drying capability produces consistent, uniform particles size and morphology, bioavailability and stability are enhanced, both of which are essential to enable advanced formulations.
Overall, spray drying enhances formulation properties, stability, and bioavailability across a wide range of dosage forms, such as:
In summary, spray drying is essential for producing high-quality, stable, and effective pharmaceutical products, enabling advanced drug delivery systems and efficient manufacturing processes.
Ascendia Pharmaceutical Solutions is your CDMO for spray drying in different environments. Our expertise, including transitioning formulations from non-cGMP to cGMP environments at small or pilot scale, allows for a seamless transition to pharmaceutical companies for larger scale production.
Do you have a pipeline candidate, but the available API is limited for formulation development? Has your current formulation project not yet scaled up or not been able to garner interest elsewhere due to its small batch size? If either is applicable, please bring them on and contact us. We’ll provide a Fast, Flexible, and First Time Right solution!