Polymorphism carbamazepine

F. Tian, J.A. Zeitler, C.J. Strachan, D.J. Saville, K.C. Gordon and T. Rades, Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy, J. Pharm. Biomed. Anal, 40, 271-280 (2006). 

L.E. O Brien, P Timmins, A.C. Williams and P. York, Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs, J. Pharm. Biomed. Anal., 36, 335-340 (2004). 

Matsuda, Y., Akazawa, R.,Teraoka, R., and Totsuka, M. (1994), Pharmaceutical evaluation of carbamazepine modifications Comparative study of photostability of carbamazepine polymorphs by using fourier-transformed reflection-absorption infrared spectrocopy and colorimetric measurement, / Pharm. Pharmacol., 46,162-167. 

McGregor, C. Saunders, M.H. Buckton, G. Saklatvala, R.D. The use of high-speed differential scanning calorimetry (Hyper-DSC ) to study the thermal properties of carbamazepine polymorphs. Thermochim. Acta 2004, 417, 231-237. 

The induction times of carbamazepine polymorphs [monoclinic, CBZ(M) and trigonal, CBZ(Trg)] were evaluated by optical microscopy. The polymorphs were identified by their crystal morphology where CBZ(M) crystallizes as prismatic crystals and CBZ(Trg) crystallizes as needles, which were confirmed by X-ray powder diffraction. It was determined that under constant supersaturation concomitant crystallization is favored in solvents that accept and donate hydrogen bonds (ethanol, methanol, isopropanol, etc.). However, the metastable CBZ(Trg) polymorph preferentially crystallized in solvents that primarily accept hydrogen bonds (ethyl acetate, methyl acetate, 2-butanone, etc.) with the stable CBZ(M) polymorph crystallizing at least an hour later. The induction times of CBZ polymorphs did not decrease with increases in solubility, suggesting that nucleation is not controlled by solubility differences. It was determined that CBZ polymorph nucleation was governed by the specific solute-solvent interactions that occurred in solution to... 

Crystallization General Principles and Significance on Product Development Table 5 Nomenclature for anhydrous carbamazepine polymorphs... 

Kaneniwa, N. Ichikawa, J.-I. Yamaguchi, T. Hayashi, K. Watari, N. Sumi, M. Dissolution behavior of carbamazepine polymorphs. Yakugaku Zasshi 1987, 107, 808-813. 

Bettini R, Bonassi L, Castoro V, et al. Solubility and conversion of carbamazepine polymorphs in supercritical carbon dioxide. Eur ] Pharm Sci 2001 13(3) 281-286. 

Figure 15. Solvent-mediated transformation of carbamazepine polymorphs in ethyl acetate at 25 °C and initial c/Sf , hi = 2.0. Reprinted from Kelly, 2003 with permission. (See color insert after Index.)...

In the case of carbamazepine polymorphs, a similar approach has been adopted to calculate dPjdT for the transition from literature solubility data (7). At least three polymorphic forms of carbamazepine have been identified form I (trigonal or a form mp 174-176°C), form II (triclinic or y form mp 184-186°C), and form III (monoclinic or (5 form mp 189-191 °C). Polymorphs I and III are enantiotropically related with a transition temperature of 71 °C (8). The former polymorph has a significantly higher solubility in supercritical carbon dioxide than the latter at 55 °C and 350 bar (9). In contrast to the negative value of dPjdT observed for the salmeterol xinafoate polymorphs, Edwards et al. obtained a positive dPjdT value (-1-23.7 bar/K) based on calculations from the carbamazepine monoclinic ((3 form) and triclinic (y form) equilibrium curves (7). The transition temperature of the... 

Figure 7 Carbamazepine polymorphs processed by SEDS at different operating temperatures and pressures using dichloromethane as solution solvent and a flow rate of 0.5 mL/min. (From Ref. 7, Copyright 2001 Wiley-Liss Inc. and American Pharmaceutical Association.)...

LE McMahon, P Timmins, AC Williams, P York. Characterization of dihydrates prepared from carbamazepine polymorphs. J Pharm Sci 85 1064-1069, 1996. 

T. Umeda, N. Ohnishi, T. Yokoyama, K. Kuroda, T. Kuroda, E. Tatsumi, and Y. Matsuda, Kinetics of the thermal transition of carbamazepine polymorphic forms in the solid state [in Japanese], Yakugaku Zasshi 104, 786-792(1984). 

Form diversity Carbamazepine Polymorph/solvate formation leading to low solubility form Pharmaceutical salts or co-crystals that are less prone to form conversion... 

The choice of polymorph before granulation determines the dissolution rate. Otsuka et al. (26) found that the use of carbamazepine polymorphs I and IV, which are the respective anhydrate and dihydrate forms, gave rise to a higher dissolution rate than polymorphs II and III, which are the anhydride forms, when hydroxypropylcellu-lose solution was employed as binder. This was because the tablets made from polymorphs I and rv were not as hard and thus disintegrated faster upon contact with the... 

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