Chemistry Reference
In-Depth Information
Figure 3.5.
Final efavirenz crystallinity as a function of PVP content at 72
°
C/52% RH
storage (error bar represents one standard deviation). (Reproduced with permission from
Ref. 55. Copyright 2010, Elsevier.)
conditions can provide signi
cant information on the minimum polymer concentration
needed to maintain physical stability; it is likely that the same amount of polymer would
provide protection under more normal handling conditions used in development.
3.2.3 Screening Methods
While it is important to determine the
final large-scale preparation method, the goal of the
screen is to cover a wide dispersion space using various polymers, solvents, ratios, and
conditions to produce stable amorphous solid dispersions. This concept is similar to
covering a wide crystallization space during a polymorph screen [56]. The screen should
be considered a search for viable amorphous solid dispersions and not necessarily a
search for a process. This implies that a variety of techniques be incorporated into the
screen to widen the possibility of
finding a suitable material for development. Other
factors, such as time and material, may limit the number of experiments that are possible
in initial early screens. It is advisable to start with the simplest formulation containing a
polymer and the API, and a range of API:polymer ratios should be incorporated into the
experimental plan. However, additional screens can be performed as the compound
moves through development to widen the dispersion screening experiments and to
nd a
material that provides better characteristics and properties for later more complex
formulations.
This section will focus on melt and solvent-based methods; it is not meant to be a
comprehensive list of experimental methods but a guide to illustrate options using these
methods.
For melt methods, it is important to evaluate the
melting properties of the components and ensure that
3.2.3.1 Melt Techniques
there is no decomposition
