3-Hydroxy-2-naphthoates of Lidocaine, Mepivacaine, and Bupivacaine and Their Dissolution Characteristics

3-Hydroxy-2-naphthoates of lidocaine (I), mepivacine (II), and bupivacaine (III) were prepared as a potential means of prolonging the action of these local anesthetic amines through their sparingly soluble salt forms. The molar ratio of the local anesthetic base to 3-hydroxy-2-naphthoic acid (IV) was 1 : 1 and the hydroxynaphthoates contained no solvent of crystallization. Dissolution characteristics of these hydroxynaphthoates were determined in water and 0.7M phosphate buffer, pH 7.46 at 37°and compared with those of the corresponding bases. The hydroxynaphthoates of I and II exhibited lower equilibrium solubilities but their dissolution rates were greater than the corresponding bases in these media. As for III, the hydroxynaphthoate showed higher solubility than the base in water.