Development of Spray Drying Processes Grounded on Innovative Approaches

New BCS Class 2 drugs represent up to 70% of the pharmaceutical pipeline. Limited aqueous solubility has been one of the major hurdles in the development of oral-dosage forms, as poor solubility hinders oral bioavailability. Different formulation strategies and enabling technologies have been used to overcome low aqueous solubility, including complexation with other compounds, nano-milling and amorphous solid dispersions (ASD).
ASDs have emerged has one of the preferred methods to improve solubility, with industrially demonstrated processes and multiple approved treatments. Generally, the ASDs manufacturing methods are classified into solvent-based – spray drying (SD), electrospraying, rotary evaporation – and melting or fusion – hot-melt extrusion, KinetiSol, Three-dimensional (3D) printing [1].

The selection of the most suitable method depends on the nature of the API and the SD has been unanimously recognized as the leading technology due to not only the mild processing conditions but also due to scalability, commercial scale representative ASD material can be produced in laboratorial scale and kept across scales [2].

The SD process development for the ASD manufacturing plays an important role throughout the development phase since it is important to ensure that all batches used in clinical trials present similar properties and quality. Thus, the transition from laboratorial to commercial scale must be driven by best practices and based upon proven methodologies for process development and scale-up. Considering the easiness and representativeness of the laboratorial scale most of the development data can be gathered at this stage aiming to:

- Increase process knowledge on solution and powder thermal stability, while establishing scale independent correlations.
- Take advantage of a wide range of analytical methods, tools, general process knowledge and historical data that enables the identification of the most adequate models for the manufacturing space and define atomization conditions:
- Improvement of modeling tools by increasing the accuracy in the prediction of SD process parameters as well droplet size (DS) by coupling rheological characterization and Phase Doppler Particle Analyzer (PDPA). This approach allows the measurement of the DS generated at the nozzle while running the process.
• Perform preliminary assessment from a quality risk management perspective following QbD principles to establish as a reliable industrial process.
Besides the data generated at laboratorial scale, prior knowledge at commercial scale needs to be considered while framing the risk management strategy to establish the manufacturing design space and accelerate drug development while minimizing the global program risk.
Thus, during this presentation the SD process development methodology and how to leverage years of industrial experience, mathematical models and complementary characterization tools to guarantee a lean material sparing and scale-up methodology will be further explained. A special focus will be given to the data generated at laboratorial scale, such as feed solution and formulation impact, atomization challenges, SD scale-independent correlations as well as to the risk management tools added value when transferring processes across scales.

[1] Sonal V. Bhujbal et al, Acta Pharmaceutica Sinica B 11 (8), 2505 (2021)
[2] Mendonsa et al, J Drug Deliv Sci Technol. 55 (2020)