Acid precipitation, driving force

The need for low levels of 3-isomer in 2-thiophenecarboxyhc acid [527-72-0] which is produced by oxidation of 2-acetylthiophene [88-15-3] and used in dmg appHcations, has been the driving force to find improved acylation catalysts. The most widely used oxidant is sodium hypochlorite, which produces a quantity of chloroform as by-product, a consequence that detracts from its simplicity. Separation of the phases and acidification of the aqueous phase precipitate the product which is filtered off. Alternative oxidants have included sodium nitrite in acid solution, which has some advantages, but, like the hypochlorite method, also involves very dilute solutions and low throughput volumes. 

Aqueous reactions can be grouped into three general categories, each with its own kind of driving force precipitation reactions, acid-base neutralization reactions, and oxidation-reduction reactions. Let s look briefly at an example of each before studying them in more detail in subsequent sections. 

Since transport across the biological membrane of weak bases will be more pronounced in the small intestine (uptake of the unionized form), sufficient precipitation inhibition (polymer) is required upon transfer of the supersaturated solution to the intestine. Therefore, one cannot rely on dissolution studies at constant acidic pH to predict the performance of formulations of weak bases in vivo (Miller et al. 2007). For instance. Six et al. (2005) observed a discrepancy between the results of in vitro dissolution tests in acidic medium and in vivo absorption for four solid dispersions of ITR faster release and increased supersaturation in acidic medium correlated with lower bioavailability. Presumably, this effect can be explained by differences in crystallization rate upon transfer to the small intestine (increased driving force for precipitation in case of higher supersaturation). Thus, it is crucial to simulate the GI pH shift during supersaturation dissolution testing of weak bases to evaluate whether supersaturation is maintained in the small intestine. 

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