Chemistry Reference
In-Depth Information
will be important for all molecules and it is important to collect relevant data for the
system being studied.
After initial assessment of the screening samples, certain
samples will be chosen for further study and more material will be needed. The amounts
can range from a couple of grams to tens or hundreds of grams. Laboratory methods such
as rotary evaporation can be used, or a move to larger scale processing such as spray
drying or melt extrusion can be used if laboratory equipment is available. These scale-up
samples can help in determining parameter ranges for large-scale production. It is
important to characterize the materials and compare back with the original properties of
the screening samples to determine whether larger batches provide the same properties
and advantages as seen previously. As with crystallization, it is not always straightfor-
ward to produce larger scale dispersions with the same properties when moving from
screening scale to laboratory/processing scale.
Drying is also an important step for solvent-based methods. Larger batches can
commonly contain a higher solvent content than smaller batches and different methods
may be needed to remove it. For spray drying, this is called secondary drying [15,70]. It is
important to use previous data to choose drying conditions that will remove solvent, but
will not cause the API to crystallize. For example, TGA data can be used to pick a
temperature where solvent will be readily removed and DSC will show whether
crystallization will occur in this temperature range
Once materials are scaled up, it is important to store them under conditions that will
maintain their amorphous nature. At this point, physical stability may not have been
assessed, or only limited information is available. In these cases, it is helpful to have
materials with a low solvent content and to store the material at about 50
3.2.3.4 Scale-Up
C below
T
g
and
at reduced RH conditions to prevent water uptake from the atmosphere. As more
information becomes available, the storage requirements will change and hopefully an
amorphous solid dispersion with robust handling properties will be available.
°
3.3 AMORPHOUS SOLID DISPERSION SELECTION
3.3.1 Properties
Selection of a lead amorphous solid dispersion, and possible backup dispersions, is based
on properties needed for development and the proposed development plan for the
molecule. Questions to help determine the path forward are the following:
What do I have?
- What forms/dispersions are available?
- What are their properties?
What do I need?
- What properties are needed to move forward?
- What dosage form is targeted short (and long) term?
