Comparative Evaluation of the Photostability of Carbamazepine Polymorphs and Cocrystals

Abstract

Carbamazepine (CBZ), a widely used antiepileptic, is known to be sensitive to light. The aim of this study was to evaluate the photostabilities of three cocrystals of CBZ (CBZ−succinic acid (SUC), CBZ−saccharin (SAC) form I, and CBZ−SAC form II) illuminated with a D65 fluorescent lamp compared with those of the conventional solid forms: CBZ polymorphs (forms I, II, and III). The order of discoloration determined using a colorimetric measurement was almost consistent with that of the degradation rates estimated using Fourier-transform infrared reflection−absorption spectroscopy, and these parameters of CBZ polymorphs increased in the order of form III, form I, and form II. CBZ−SUC and CBZ−SAC form I significantly suppressed the discoloration and degradation of CBZ compared with the raw CBZ, while CBZ−SAC form II facilitated the discoloration and degradation of CBZ. These results were supported by the results from the low-frequency Raman spectroscopy. The molecular mobility estimated using solid-state nuclear magnetic resonance 1H spin−lattice relaxation time strongly correlated with the degradation rate constant, indicating that molecular mobility significantly decreased following the formation of CBZ−SUC and CBZ−SAC form I and resulted in higher photostability. Overall, CBZ−SUC and CBZ−SAC form I are photostable forms and cocrystallization was proven to be an effective approach to improving the photostability of a photolabile drug.

Keywords

• carbamazepine
• photostability
• polymorphs
• cocrystal
• succinic acid
• saccharin