Steroids, anti-inflammatory basic

Much of the beneht in solubihty enhancement from salt formation is attributable to the change in solution pH caused by the presence of the counterion. This occurs because the ionization and solubility of acidic drugs (such as barbiturates and non-steroidal anti-inflammatory drugs) increases in basic conditions but decreases in acidic conditions. This behavior is exemplified by derivations of the Henderson-Hasselbalch equations (37.2) and (37.3). The opposite situation occurs for basic drugs such as chlorpromazine, morphine and codeine, which are more soluble in acidic conditions. 

Juni et al. (2004) carried out a cumulative meta-analysis in which they included all randomised controlled trials in patients with chronic musculoskeletal disorders that compared rofecoxib with other non-steroidal anti-inflammatory drugs (NSAIDs) or placebo (p. 2021). The outcomes targeted were cardiovascular side-effects, in particular myocardial infarctions, and they found that by the year 2000 there was already evidence of a significant effect on rofecoxib on cardiovascular health, which they interpreted as harm compared with placebo. This drew an angry response from Kim and Reicin (2004), who worked for Merck, the makers of rofecoxib, claiming that the approach contravenes the basic principle of meta-analyses to combine like with like, and thus arrives at flawed conclusions . 

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