Paracetamol crystallization

M. Fujiwara, P.S. Chow, D.L. Ma and R.D. Braatz, Paracetamol crystallization using laser backscatteiing and ATR-FTIR spectroscopy metastability, agglomeration, and control, Cryst. Growth Des., 2(5), 363-370 (2002). 

Nichols, G. and Frampton, C. S. (1998). Physicochemical characterization of the orthorhombic polymorph of paracetamol crystallized from solution. J. Pharm. ScL, 87, 684-93. [113, 144f]... 

Worlitschek, J. Mazzotti, M. Model-based optimization of particle size distribution in batch-cooling crystallization of paracetamol. Crystal Growth Design 2004, 4 (5), 891-903. 

Figure 11.15 Uptake of impurities by paracetamol crystals. (Reprinted with permission from Hendricksen, B.A., Grant, D.J. W., Meehan, P., and Green, D.A., In Crystal Growth of Organic Materials, ACS Conf. Proc. Series, Myerson, A.S., Green, D.A., Meehan, P. eds., pp. 95-104 (1996). 1996. American Chemical Society.)...

S.D. Finnic, R.O. Ristic, J.N. Sherwood, and A.M. Zikic. Morphological and growth rate distributions of small self-nucleated paracetamol crystals grown from pure aqueous solutions. J. Cryst. Growth 207 308-318,1999. 

The paracetamol crystals were submitted to four different drying conditions (Table 15.2.3.2) ... 

Determination of residual water on paracetamol crystallized in water according to the titrimetric direct method of Karl Fischer. 

The packed column was Porapack super Q (Alltech, France), mesh range 80/100, length 1.80 m, internal diameter 2.16 mm. Carrier gas anhydrous nitrogen. Injector temperature 200°C. Detector temperature 220°C. The chromatographic conditions were For dichloromethane, tetrahydrofuran and hexane in paracetamol crystals isotherm at 150°C, injection 5 0,1, RT methanol 0.8 min, dichloromethane 3 min, tetrahydrofuran 7.8 min, hexane 11.8 min. 

C, the rubbery paracetamol crystallizes into the metastable form 2, which subsequently melts at ISS C. 

FIGURE 5.9 (a) Molecular packing arrangement in paracetamol crystal structure and (b) molecular structures of the impurities. 

Generation of Paracetamol Crystals from EtOH, AC, and EtOH/AC Mixture Solutions... 

A further increase of the quantity of ethanol in the solvent blend toward a ratio of 80/20 and 90/10 wt% of EtOH to acetone, finally leads to a pure monoclinic modification I of the generated paracetamol crystals. Those two solvent mixtures are represented by the spectra (d) (80/20) and (e) (90/10) and can be compared with spectrum (f), which represents the unprocessed paracetamol in the pure monoclinic form I. This means that referred only to the crystalline modifications of PCM,... 

Paracetamol is a compound with a significant usage in the pharmaceutical industry. It is already known that the paracetamol crystal exhibits a polymorphism. Three polymorphs of paracetamol have been reported a thermodynamically stable monoclinic form I, a metastable orthorhombic form II, and a very unstable form III. The monoclinic form I is the form used commercially due to its thermodynamic stability at room temperature. In the current work, we investigate both forms I and II to underline the difference in their chemical behavior and to point out that it is not possible to gain understanding about one form based upon the knowledge on another form. 

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