Handbook of Solvents - George Wypych - ChemTech - Ventech!

988 Michel Bauer, Christine Barthélémy
Figure 14.21.1.1. DSC and TG patterns.
In order to demonstrate the internal character of the clathrate relative to the crystal lattice,
the example of a molecule developed in the laboratory of one of the authors is given below.
Figure 14.21.1.1 shows the DSC pattern of a molecule with the melting event at 254°C
and the corresponding TG pattern obtained at the same temperature scanning rate. At the
time the melting occurs, a loss of weight is observed corresponding to the loss of 0.2 % of
isopropanol. The nature and the amount of the solvent have been confirmed by GC after dissolving
the substance.
14.21.1.3.2 Drug product
As for the DS, the solvents used for DP manufacture can produce some negative effects by
themselves or through their own impurities.
For liquid or semi liquid formulations, the formulator has to ensure that the solvents
themselves do not display chemical interactions with the DS or the excipients. Everything
which has been said in paragraphs 14.21.1.2.1.5 and 14.21.1.3.1 remains true here.
14.21.1.3.2.1 Interaction of impurities contained in the solvent
As said in paragraph 14.21.1.3.1 with the DS, impurities contained in the solvent especially
if they are strongly reactive, like aldehydes or peroxides, can promote formation of
degradants. Regarding aldehydes, the publication of Bindra and all 29 should be mentioned.
It relates to the degradation of the o-benzylguanine in an aqueous solution containing polyethylene
glycol 400 (PEG 400). This type of solvent very often contains formaldehyde,
which can lead to the formation of a precipitate over time: