O

the o-position ofthe hydroxyl group as an essential steric requirement for this activity. Mechanistically, this was explained by the unique proton bridging between the oxygen of the carboxyl group and the proton in the hydroxy group, allowing for a mesomeric state that promotes a nondissociated configuration and facilitates tissue penetration [73].

Acetylsalicylic Acid Acetylsalicylic acid (molecular weight 180.2) or aspirin is the acetate ester of salicylic acid. The pharmacological properties are similar to those of salicylate. However, aspirin also has activities of its own, which are added by the reactive acetate group - the (nonselective) acetyla-tion of cellular targets, including proteins and DNA. This results in biological effects that are not shared by salicylate. Examples are the inhibition of platelet function by irreversible acetylation of COX-1 and the acetylation of COX-2 with subsequent formation of 15-(R)-HETE and generation of ATL by white-cell 5-lipoxygenases (Section 2.2.1).

Aspirin is a white powder with a pleasant acidic taste. The compound is poorly soluble in water (0.3%) and somewhat better soluble in ethanol (20%). The solubility in aqueous media depends on pH. It amounts to only 60 mg/ml at pH 2, but increases dramatically with increasing pH (Figure 1.9). The solubility in aqueous media is also markedly improved after its conversion into the sodium salt, specifically at acidic pH (Table 1.2).

aqueous solution at 42 °C. Note the high stability (poor solubility) of aspirin at acidic pH and the significant increase in solubility (rapid degradation) at alkaline pH [74].

Table 1.2 Dissolution rates of various salicylates in 0.1 N hydrochloric acid (modified after Levyand Leonards, 1966).

Dissolution rate (units at current stirring and 37 °C)

Dissolution rate (units at current stirring and 37 °C)

Table 1.2 Dissolution rates of various salicylates in 0.1 N hydrochloric acid (modified after Levyand Leonards, 1966).

Compound

Absorption

Release

Salicylic acid

Was this article helpful?

0 0

Post a comment