Acetaminophen crystallization

Figure 8 Dissolution-time profile of acetaminophen crystals (75 mg, 355-500 pm) in water at 4°C. The crystals were grown at 30°C and at 240 rpm from aqueous solutions containing initially 23.1 g/dm3 acetaminophen and the following concentrations of p-acet-oxyacetanilide a ( ) Zero ( ) 100 mg/dm3 (A) 300 mg/dm3 (O) 500 mg/dm3. (Reprinted with permission from Ref. 6.)...

AF1L Chow, PKK Chow, W Zhongshan, DJW Grant. Modification of acetaminophen crystals Influence of growth in aqueous solutions containing p-acetoxyacetanilide on crystal properties. Int J Pharm 24 239-258, 1985. 

Chow, A.PI.L. and Grant, D.J.W. (1988). Modi cation of acetaminophen crystals. III. In uence of initial supersaturation during solution-phase growth on crystal properties in the presence and absence ol p-acetoxyacetanilidipt. J. Pharm., 42 123-133. 

Green DA, Meenan P. Acetaminophen crystal habitSolvent effects. In Myerson AS, Green DA, Meenan P, eds. Crystal Growth of Organic Materials. ACS Conference Proceedings, 1996 78-84. 

Figure 11.1 Raman images created as integrated intensity maps (1310-1350cm ) from Raman maps of an acetaminophen crystal recorded at net acquisition times of (a) 100ms (red) (b) 1 s (green) and (c) 2s (blue) per spectrum Figure 11.2. The histogram of each Raman image (x-axis, Raman intensity in arbitrary units y-axis, number of spectra) is displayed next to each Raman image.

Figure 6 (a) Image of acetaminophen crystals (mean size 3 pm) obtained by precipitation from ethanol solution with CO2 and used as seeds, (b) Jet flow pattern obtained by application of autocorrelation PIV algorithm to this image. The conditions correspond to those in Figure 5. 

Figure 17 Comparison of experimental data with model predictions for mean particle size of acetaminophen crystals obtained by jet mixing, from direct CFD calculations of macromixing and supersaturation profile in Figure 16 and from mechanistic modeling (44-46), which allows for inclusion of the effects of molecular viscosity and diffusivity on rate of mixing on molecular scale (important for low Re).

Green, D. A., and P. Meenan. 1996. Acetaminophen crystal habit Solvent effects. In Crystal growth of organic materials, edited by A. S. Myerson, D. A. Green, and P. Meenan. ACS Conference Proceedings, pp. 78-84. 

Table 1 Crystal Data for Two Polymorphs of Acetaminophen Crystal data and stmcture...

Omar, W., Al-Sayed, S., Sultan, A. and Ulrich, J. (2008) Growth rate of single acetaminophen crystals in supersaturated aqueous solution under different operating conditions. 43, 22-27. 

Gas AntisolventRecrystallizations. A limitation to the RESS process can be the low solubihty in the supercritical fluid. This is especially evident in polymer—supercritical fluid systems. In a novel process, sometimes termed gas antisolvent (GAS), a compressed fluid such as CO2 can be rapidly added to a solution of a crystalline soHd dissolved in an organic solvent (114). Carbon dioxide and most organic solvents exhibit full miscibility, whereas in this case the soHd solutes had limited solubihty in CO2. Thus, CO2 acts as an antisolvent to precipitate soHd crystals. Using C02 s adjustable solvent strength, the particle size and size distribution of final crystals may be finely controlled. Examples of GAS studies include the formation of monodisperse particles (<1 fiva) of a difficult-to-comminute explosive (114) recrystallization of -carotene and acetaminophen (86) salt nucleation and growth in supercritical water (115) and a study of the molecular thermodynamics of the GAS crystallization process (21). 

HK Chan, DJW Grant. Influence of compaction on the intrinsic dissolution rate of modified acetaminophen and adipic acid crystals. Int J Pharm 57 117-124, 1989. 

More examples of forensic applications of Raman spectroscopy have been published recently. It has been used to identify individual crystals of drugs and excipients on paper currency [110], multilayer paint chips, inks, plastics [111], and fibers [112], A study demonstrated the feasibility of quantifying acetaminophen in the presence of many excipient types [113], Other studies seek to identify particulates, such as illicit or abused drugs, in fingerprints lifted at a crime scene [114,115]. 

From what we see on the next page (properties) we can tell that codeine is not very soluble, so it stands to reason that this will be the last substance that will be eluted from the column. Acetaminophen looks the most soluble, so lets get rid of it first. Acetone looks like a good choice, but its hard to tell because the Merck Index did not say if the other substances are soluble or insoluble in acetone. Try a little and see what types of crystals appear upon evaporating off the solvent, test the melting point and see if it is exactly as stated for acetaminophen. If there are only two types of crystals then it may be easier to go ahead and elute these and then separate... 

Grant, D. J. W. and Chow, A. H.-L (1991) Crystal modi cations in acetaminophen by growth from aqueous solutions containinjp-acetoxyacetanilide, a synthetic impurity,ChE Symp. Ser., 284 33-37. 

Tylenol CH3CONHC6H4OH N-acetyl-p-aminophenol (acetaminophen, APAP) colourless, slightly bitter crystals can be toxic if an overdose is taken pain reliever (analgesic)... 

Boldyreva, E. V., Shakhtshieder, T. P, Vasilchenko, M. A., Ahsbahs, H. and Uchtmann, H. (2000). Anisotropic crystal structure distortion of the monoclinic polymorph of acetaminophen at high hydrostatic pressures. Acta Crystallogr. B, 56, 299-309. [239]... 

Ziller, K.H. Rupprecht, H. Control of crystal growth in drug suspensions 1. Design of a control unit and application to acetaminophen suspensions. Drug Dev. Ind. Pharm. 1988, 14, 2341-2370. 

Fig. 15 shows an example of the direct design approach implemented for the isothermal antisolvent crystallization of acetaminophen (paracetamol) from acetone-water mixture. A constant relative supersaturation (Ac/c ) setpoint profile was followed. The flow rate setpoint of the antisolvent was calculated every minute based on the solution concentration measured using the IR spectra so that a setpoint supersaturation profile was followed. The change in solution concentration and antisolvent flow rate during the batch is shown in Fig. 16. After an initial start-up...

Fig. 15 Direct design approach using concentration measurement for seeded antisolvent crystallization of paracetamol (acetaminophen) from acetone-water mixture. The concentration-% solvent profile of the batch, the setpoint profile, and the solubility curve are shown. The setpoint followed is that of a constant relative supersaturation Ac/c = 0.04 g/mLsolvent+antisolvent"...

Fig. 10 SEM images of unprocessed and SEDS-processed acetaminophen. (A) As received from Sigma Aldrich, 200x magnification. (B) Crystals manufactured by the SEDS process at 40° C, 150 bar pressure, using a feedstock of lOmg/ml acetaminophen in ethanol. (SEM courtesy of S. Desikan, Bristol-Myers Squibb processing by S. Jen and P. Stetsko, Bristol-Myers Squibb.).

Crystals of the amide known as acetaminophen (Tylenol) viewed under polarized light. The stracmre of acetaminophen is... 

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