Effect of Droplet-Wake Phenomena on Mixing-Sensitive Pharmaceutical Reactions - Pharmaceutical Technology

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Effect of Droplet-Wake Phenomena on Mixing-Sensitive Pharmaceutical Reactions

Pharmaceutical Technology

Figure 2
in which A is the liquid-phase reactant, G is the dissolving gas, P is the product, and BP the byproduct (19). This could be a generic network corresponding to a hydrogenation and overhydrogenation. A typical result of our study is shown in Figure 3, which plots the selectivity Y P toward the reaction as a function of the bubble Reynolds number. The initial decrease of Y P coincides with the onset of recirculation. Recirculation leads to a significantly increased residence time of the product P in the wake and reduces the concentration of the reactant A in the wake. Effectively, the recirculating pattern in the wake acts as a barrier for reactant A, which cannot enter the wake. Thus, because the concentration of A is low, a larger fraction of the gas G reacts with P to form the secondary product BP, leading to a decrease of the selectivity. At Reynolds numbers greater than 52, vortex shedding occurs, which causes a sudden increase of selectivity (see Figure 3). Once vortex shedding occurs, patches of the dissolved gas G (and product P) are quickly convected away from the bubble into regions rich in A, thus leading to significantly higher selectivities toward P. In effect, the transition from a closed wake to an open wake qualitatively changes the mixing behavior, which can lead to a large change in the reaction selectivity.

Figure 3
This study involves a similar reaction network to prove our computational results experimentally. For safety reasons, however, a liquid–liquid system was chosen in favor of a gas–liquid reaction.


Reaction and chemicals. To verify the computationally predicted effects previously published (19–22), an extensive series of experiments was performed. The iodination of l-tyrosine to form 3-iodo-l-tyrosine and 3,5-diiodo-l-tyrosine was studied in a liquid–liquid system. This is a competitive-consecutive second-order reaction, previously studied in a single liquid phase by Paul and Treybal (11), that occurs naturally within the human body. The compound l-tyrosine aids in the production of thyroid hormones by acting as a carrier and allowing iodine to enter the thyroid cells. Figure 4 shows the reaction system.

Figure 4
We purchased 98% pure l-tyrosine from Sigma Aldrich (St. Louis, MO). Samples of 3-iodo-l-tyrosine and 3,5-diiodo-l-tyrosine were also purchased from Sigma Aldrich for use as standards for high-performance liquid chromatography (HPLC). All other chemicals (sodium hydroxide, potassium iodide, iodine, sodium phosphate dibasic, sodium phosphate tribasic dodecahydrate, methylene chloride, and glycerin) were purchased from either Fisher Scientific or Sigma Aldrich and were a minimum of 98% pure.


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