Chemistry Reference
In-Depth Information
Figure 2.15.
Flow diagram of the SPADS screening process. Only promising polymers and drug
loadings advance to each subsequent stage. (Adapted from Ref. 90.)
In an effort to streamline the polymer selection process for ASDs and minimize time
and resources, Hoffmann-La Roche introduced a miniaturized method that is referred to
as screening of polymers for amorphous drug stabilization (SPADS) [25b,90]. The
SPADS method is a three-stage process, outlined in Figure 2.15, in which amorphous
films consisting of at least seven polymers and multiple drug loadings are prepared. In the
films is assessed in 96-well plates. Polymers and drug
loadings that demonstrate improved API solubility and supersaturation are then sub-
jected to an imaging assay utilizing atomic force microscopy to determine molecular
homogeneity of the ASD and an interaction assay via FTIR to investigate intermolecular
interactions. ASDs of polymers and drug loadings that have favorable interactions and
molecular homogeneity are then prepared via spray drying and tested with traditional
dissolutions studies and 6-month stability studies [90].
first step, the dissolution of the
2.4.4 Stability of Amorphous Solid Dispersions
Due to the nature of ASDs in which the API is molecularly dispersed within the carrier
surfactant or polymer matrix, there is an increased chance of physical interaction between
the two species. Careful evaluation of an ASD must occur to ensure that it is both
chemically and physically stable to ensure that the desired performance of the ASD is
achieved and maintained. A general method of screening for chemical stability and
