Acetylsalicylic acid crystallization

Miyasaka E, Kato Y, Hagisawa M, Hirasawa I (2006) Effect of ultrasonic irradiation on the number of acetylsalicylic acid crystals produced under the supersaturated condition and the ability of controlling the final crystal size via primary nucleation. J Cryst Growth 289(1) 324—330... 

Enteric Film Coating of Acetylsalicylic Acid Crystals (Aqueous)... 

Enteric Film Coating of Acetylsalicylic Acid Crystals (Aqueous) page 2 3. Coating procedure (Fluidized bed, Aeromatic Streal)... 

If you let your crystals dry overnight, then find your safety glasses again and put them on. Take about a quarter of either the wet or dry acetylsalicylic acid crystals and place them into a glass container that can be used for warming. The dried crystals are very fluffy and should be handled carefully so they do not scatter. Take the bottle of aquarium pH-lowering solution recommended for purchase in the Shopping List and Solutions, and add it dropwise until the entire sample of acetylsalicylic acid is com-... 

Calculations of the spectra of the closely related compounds—acetylsalicylic acid (aspirin) and salicylaldehyde, at different temperatures and with selective deuteration, have been published for acetylsalicylic acid in Ref. 54 and for salicylaldehyde in Ref. 53. In the acetylsalicylic acid crystal there are no intramolecular hydrogen bonds—only intermolecular hydrogen bonds are present. The molecules of acetylsalicylic acid form hydrogen-bonded dimeric cyclic structures, similar to those present in salicylic acid. The IR spectra of the acetylsalicylic acid and the salicylic acid crystals in the region of the O—H(D) stretching vibrations are similar, excluding peaks due to intramolecular hydrogen bonds. Spectra of the acetylsalicylic acid crystal were calculated at two temperatures 300 and 77K. The experimental spectra and the observed temperature and isotopic effects are reproduced in these calculations reasonably well [54]. 

The preparation of an ion-selective electrode for salicylate is described. The electrode incorporates an ion-pair of crystal violet and salicylate in a PVC matrix as the ion-selective membrane. Its use for the determination of acetylsalicylic acid in aspirin tablets is described. A similar experiment is described by Creager, S. E. Lawrence, K. D. Tibbets, C. R. in An Easily Constructed Salicylate-Ion-Selective Electrode for Use in the Instructional Laboratory, /. Chem. Educ. 1995, 72, 274-276. 

The reaction mixture is now transferred to aluminum cooling tanks, and is allowed to cool slowly, over a period of 3 to 4 days, to a terminal temperature of 15-25°C (room temperature). The acetylsalicylic acid precipitates as large, regular crystals. The mother liquor is now filtered or centrifuged from the precipitated acetylsalicylic acid and the filter cake is pressed or centrifuged as free of mother liquor as possible. The crystals are washed with distilled water until completely free of acetic acid, pressed or centrifuged as dry as possible and the filter cake is then dried in a current of warm air at a temperature of 60-70°C. 

To form aspirin, the salicylic acid is refluxed with acetic anhydride in toluene at 88 to 92°C for 20 hours. The reaction mixture is then cooled in aluminum cooling tanks, and the acetylsalicylic acid precipitates as large crystals that are separated by filtration or by centrifugation, washed, and dried. 

Add 10 mL of 95% ethanol to the mortar and continue to grind for 2 min. Place a filter paper (Whatmann no. 2, 7 cm) in a funnel and place the funnel in a 250-mL Erlenmeyer flask. With the aid of a glass rod, transfer the supernatant liquid from the mortar to the filter paper. After a few minutes, when about 1 mL of clear filtrate has been collected in the Erlenmeyer flask, lift the funnel and allow a drop of the filtrate to fall on a clean microscope slide. Replace the funnel in the Erlenmeyer flask and allow the filtration to continue. The drop on the microscope slide will rapidly evaporate leaving behind crystals of acetylsalicylic acid. This is a qualitative test showing that the extraction of the active ingredient is successful. Report what you see on the microscope slide on your Report Sheet (3). 

ASA CH3COOC6H4COOH o-acetoxy benzoic acid (acetylsalicylic acid) white crystals with a slightly bitter taste excessive use may cause hearing loss or Reye s syndrome, especially in young people used in Aspirin and related medicines for pain, fever, and inflammation... 

A flow diagram for the production of aspirin is shown in Fig. 10.6 [9]. A mixture of salicylic acid powder, acetic anhydride, and a small amount of sulfuric acid is charged into a batch reactor. The mixture is stirred for 2 to 3 hours and then transferred to a crystallizing kettle. A portion of the mother liquor is recycled in the next run, and the other part of the slurry is centrifuged. The resulting crystalline material is dried in a rotary drier to yield acetylsalicylic acid (aspirin). Excess mother liquor is distilled and the excess of acetic anhydride is recycled. 

Goczo, H. Szabo-Revsez, P. Farkas, B. Hasznos-Nezdei, M. Serwanis, S.F. Pintye-Hodi, A.K. Kasa, P., Jr. Eros, I. Antal, I. Marto, S. Development of spherical crystals of acetylsalicylic acid for direct tablet-making. Chem. Pharm. Bull. 2000, 48 (12), 1877-1881. 

Such a singularity is clearly visible on the Arrhenius curve of Aciass determined for a crystal of acetylsalicylic acid-iV, 8. In Fig. 17 this curve is compared with those for the values of and k, determined recently for the same system cf. Subsection 4.2). 

In the latter paper, a throughout NMR study on a single crystal of acetylsalicylic acid selectively C-labelled in the methyl group is also reported. Despite the fact that in the temperature range investigated condition (ii) is perfectly fulfilled for the above material (at that range, the values of A approach 300 MHz), the observed spectra cannot be interpreted in terms of the AB model unless one admits that below 25 K the values of A ciass increase with further decrease of temperature. It must be stressed that use of the DQR instead of the AB model would offer no help to rationalize that strange behaviour in the limit of Id/Al 1, where d = max[ld( H- H)l, H)l], the calculated spectra are insensitive to... 

Fig. 18. Experimental NMR spectra of a single crystal of acetylsalicylic acid selectively C-labelled in the methyl group. At 25 K, the stochastic dynamics are slowed down such that features characteristic of the pattern in the limit of Id/ AI

Pedersen S, Kristenen HG. Change in crystal density of acetylsalicylic acid during compaction. SEP Pharma Sci 1994 4 201-206. 

Bundgaard, H. Influence of an acetylsalicylic anhydride impurity on the rate of dissolution of acetylsalicylic acid. J. Pharm. Pharmacol. 1974, 26, 535-540. Klug, D.L. The influence of impurities and solvents on crystallization. In Handbook of Industrial Crystallization Myerson, A.S. Ed. Butterworth-Heinemann Boston, 1993 65-87. 

A) Structure of the drug sulfadimidine 9 and (B) hydrogen-bonded molecular complex between sulfadimidine and acetylsalicylic acid (aspirin) in the co-crystal. 

Figure 3.8 (a) Packing diagram of carbamazepine.formic acid solvate and (b) packing diagram of carbamazepine acetylsalicylic acid co-crystal... 

Over one-half of the salicylic acid is used to manufacture acetylsalicylic acid, quantitatively one of the most important analgesic pharmaceuticals. Acetylsalicylic acid was first produced in 1853 from acetyl chloride and sodium salicylate. Its introduction as a medicament occurred in Germany in 1899 (Aspirin) and in the USA in 1900. Acetylsalicylic acid is now produced by reaction between salicylic acid and acetic anhydride in stainless steel or enamelled reactors at a temperature below 98 °C (duration of reaction 2 to 3 hours). The reaction mixture is refined by crystallization at 0 °C. 

The crystal structure of the 3 cyclodextrin (3-CyD) molecular complex with aspirin (acetylsalicylic acid), salicylic acid, and water, (0 2 70 35)2 ( 7 6 s) 23.3H2O, was determined by X-ray... 

When the reaction is complete, some unreacted salicylic acid and acetic anhydride will be present, along with acetylsalicylic acid, acetic acid, and the catalyst. The technique used to purify the acetylsalicylic acid from the other substances is called crystallization. This technique, which was introduced in Experiment 3, will be studied in more detail in Experiment 11. The basic principle is quite simple. At the end of this reaction, the reaction mixture will be hot, and all substances will be in solution. As the solution is allowed to cool, the solubility of acetylsalicylic acid will decrease, and it will gradually come out of solution, or crystallize. Because the other substances are either liquids at room temperature or are present in much smaller amounts, the crystals formed will be composed mainly of acetylsalicylic acid. Thus, a separation of acetylsalicylic acid from the other materials will have been accomplished. The purification process is facilitated by the addition of water after the crystals have formed. The water decreases the solubility of acetylsalicylic acid and dissolves some of the impurities. 

This reaction is carried out in batch reactors at about 90 °C. Salicylic acid (SA), acetic acid (HoAc), and acetic anhydride (AA) are charged to the reactor initially. After 2-3 h of reaction, the contents of the reactor are discharged to a crystallizer to recover the acetylsalicylic acid (ASA). 

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