Slow-release effect of pH-adjusted bupivacaine: In vitro demonstration

Abstract

Commercial solutions from the same lot of 0.25% bupivacaine (pH = 5.69 ± 0.02) were studied before, and at 3 min and 12 h after alkalinization with 0.4 mEq. sodium bicarbonate/20 ml (final pH = 7.39 ± 0.01). An in vitro dissolution method was modified from a previously described technique used to measure the slow-release effect of insulin suspensions. Alkalinization resulted in a significant increase in the number of crystals of bupivacaine base and in the prolongation of bupivacaine release from the crystals. The results are in agreement with several clinical reports in which prolonged duration of the sensory block was observed. The extent of adsorption on the walls of glass bottles and of plastic syringes increased with the duration of contact after alkalinization. The adsorbed fraction of bupivacaine therefore could not participate in producing the expected clinical effect and might explain several unsuccessful attempts at pH adjustment.