Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS™)

Self-built Supercritical CO2 Anti-solvent Unit Design, Construction and Operation using Carbamazepine

“…Combining both the XRPD and DSC results, it is reasonable to infer that more than one CBZ crystalline forms coexisted in the treated samples with the predominant polymorph being Form III. Such co-existence of different CBZ crystalline forms after SAS CO 2 treatment is very much in agreement with previous reports (20,26,28). The recrystallisation process prevents direct measurement of the enthalpy and quantification of low levels of different forms, especially the higher melting Form I in mixtures of the CBZ crystals is not possible (24).…”

“…3 untreated). These values compare well with the simulated XRD patterns, with the at least one small shift resulting from the different XRD sampling temperatures for data collection (20,27). However, the intensities vary, especially for form III, which is possibly due to the orientation of powder in the X-ray sample holders as has been reported by other groups (20,27).…”

“…In general, a higher operational temperature can either vaporize the organic solvent easily to achieve a higher degree of supersaturation, or increase the solute solubility and there- The yields were calculated using the weight of generated particles divided by the input weight of untreated carbamazepine fore impede the precipitation of particles (20,(22)(23)(24). According to our results, the effect of temperature seemed to prevail in practice.…”

“…4 (treated) corresponded with the different polymorphic forms of CBZ that have emerged after SAS CO 2 treatment with the unchanged Form III predominating as indicated by the endotherm onset at 164.77°C and the large peak at 192.41°C. The large endotherm observed with an onset of 190.45°C may also be due to the melting of Form I, although it is important to keep in mind that it is possible for Form III to change to Form I when heated and the re-crystallization of Form I from the melt of Form III can be overwhelmed by its melting peak (20). The endothermic peak at 157°C is in agreement with the reported thermal data of Form II whereas the endothermic peak emerging at around 185°C corresponds with Form IV.…”

“…Indeed, Carbamazepine particle's micronization using SAS method has been investigated by several research groups in the past and their data indicated that particle size reduction is possible and different polymorphic or amorphous forms could coexist in the final product (19)(20)(21). However, none of the previous studies have managed to relate the particle yield and characteristics with the processing conditions, e.g.…”