Dissolution of bupivacaine 3-hydroxy-2-naphthoate into phosphate buffers

Dissolution behaviour of bupivacaine 3-hydroxy-2-naphthoate (BUPNH) into phosphate buffers, pH 7.4 was investigated at 25 degrees and 37 degrees C. Although the dissolution pattern of the salt at 25 degrees C was normal, i.e., the concentrations of the acid and base component agreed, during the entire dissolution period, that at 37 degrees C was anomalous. The dissolution consisted of two phases, i.e. an initial normal phase was followed by a second slower phase in which the concentration of the acid became, at equilibrium, markedly higher than that of the base. This unusual dissolution behaviour at 37 degrees C was shown to be due to the precipitation of the base, which, in turn, is attributed to the unusual temperature dependency of the solubility of the base in phosphate buffers, i.e. decrease in solubility with increasing temperature.