Can Storage Time Improve the Physical Stability of Amorphous Pharmaceuticals with Tautomerization Ability Exposed to Compression? The Case of a Chloramphenicol Drug.

In this article we thoroughly investigated the physical stability of the amorphous form of a chloramphenicol drug. The tendency toward recrystallization of this drug has been examined (i) at nonisothermal conditions by means of a DSC technique; (ii) at isothermal conditions and temperature close to T _room by means of dielectric spectroscopy; (iii) at isothermal conditions and elevated temperatures of T = 323 K and 338 K by dielectric spectroscopy; and (iv) at conditions imitating the manufacturing procedure (i.e., elevated temperature and compression procedure). Our investigations have shown that amorphous chloramphenicol, stored at both standard storage and elevated temperature conditions, does not reveal a tendency toward recrystallization. However, compression significantly changes this behavior and destabilizes the examined compound. We found that due to chemical equilibration of the sample, the elongation of the storage time before compression might improve the physical stability of the examined pharmaceutical exposed to compression 34-times.