Choosing the right technique
PTE: One tool for bioavailability enhancement is to create amorphous solid dispersions through processes such as hot-melt extrusion (HME) or spray drying. What factors come into play to decide whether to produce the amorphous solid dispersions through HME or spray drying?
The processing temperature is important for HME because the API must either melt to form a dispersion or dissolve through high shear forces into the molten polymer. If the processing temperature is too high, the compound or the polymer used in the formulation can degrade. Typically, 200 °C to 225 °C is regarded as the upper processing-temperature limit for an effective HME process. Although compounds can be extruded at higher processing temperatures, this physical situation often produces a partially crystalline formulation instead of an amorphous dispersion.
The phase of development is also an important factor in process selection. For example, for early-stage or discovery-support activities, API availability is often limited. This limited API availability tends to make spray drying the preferable process because its feasibility can be determined with as little as 50 to 100 mg of API, whereas several grams of API are typically required to develop an initial HME process. For APIs that are amenable to HME, typically after proof-of-concept clinical studies, when hundreds of grams of API are available, an initial spray-drying process can be converted from spray drying to HME.