Revealing the early stages of carbamazepine crystallization by cryoTEM and 3D electron diffraction

Time-resolved carbamazepine crystallization from wet ethanol has been monitored using a combination of cryoTEM and 3D electron diffraction. Carbamazepine is shown to crystallize exclusively as a dihydrate after 180 s. When the timescale was reduced to 30 s, three further polymorphs could be identified. At 20 s, the development of early stage carbamazepine dihydrate was observed through phase separation. This work reveals two possible crystallization pathways present in this active pharmaceutical ingredient.

PREPARATION AND EVALUATION OF CO-CRYSTALS OF CARBAMAZEPINE WITH GLUCOMANNAN

Objective: The objective of the present work was to inhibit transformation of carbamazepine anhydrous to its dihydrate form in aqueous medium by adopting the co-crystal approach.Methods: Co-crystallization of carbamazepine and glucomannan as co-former was carried out by solution mediated phase transformation. The solution of carbamazepine and glucomannan in ethanol (95%) was agitated for 2 h and the co-crystals obtained were recovered after 24 h.Results: Co-crystal formation due to hydrogen bonding between carbamazepine and glucomannan as a co-former was confirmed by FTIR study. Inhibition of transformation of co-crystal of carbamazepine to carbamazepine dihydrate in aqueous medium was confirmed by SEM.Conclusion: Inhibition of transformation of carbamazepine co-crystal to its dihydrate form resulted in its improved dissolution. Dissolution efficiency of carbamazepine in its co-crystal was increased up to 79.26% within 30 min.

Quantitative analyses of complex pharmaceutical mixtures by the Rietveld method

The object was to perform simultaneous quantitative analyses of complex pharmaceutical solid mixtures by the Rietveld method. Mixtures consisting of anhydrous β-carbamazepine, anhydrous α-carbamazepine, and carbamazepine dihydrate were chosen as the model system. Lithium fluoride was used as the internal standard. Mixtures of various compositions were prepared and subjected to X-ray powder diffractometry (XRD). The XRD pattern of each mixture was analyzed by the Rietveld method and at the end of the refinement, the goodness of fit was evaluated. When the analyte concentration was high (≥20%), the relative error in the determination was <±5%. The detection of analyte was possible even when its concentration was low (<1% w/w). A unique advantage of the method is that it enables simultaneous quantitative analyses of multiple phases without the requirement of “standard curves.” © 2001 International Centre for Diffraction Data.