Critical Process Parameters for Spray Drying Pharmaceuticals

During the manufacturing of an oral pharmaceutical solid dosage form (e.g. tablets or capsules), the active pharmaceutical ingredient (API) is combined with one or more excipients and transformed into a process intermediate. These intermediates improve the manufacturability of the final solid dosage product or enhance the bioavailability of the API. For example, spray dried intermediates (SDI) are often produced for delivering the small molecule API in the amorphous form, with the intent of increasing the apparent solubility. Understanding the relation between the process intermediates and the process parameters is essential for identifying the risks, establishing a working operating space and scaling up. However, these processing techniques are based on rich and complex multi-scale, multi-phase physics. Currently, analytical techniques are used to better define the properties of the generated process intermediates, including chemical (e.g. composition), physical (e.g. amorphous phase or certain crystalline phase/polymorph), or structural/textural information (e.g. porosity or pore size distribution). These properties may impact downstream processability, storage conditions, and most importantly performance. Over the past 10 years, the industry has seen a huge increase in the use of spray drying technology. However, the relationships between the critical processing parameters on the critical quality attributes remains ill defined. This work will aim to fill this unmet need.