Bupivacaine hydrochloride complexation with some α- and β-cyclodextrins studied by potentiometry with membrane electrodes

Abstract

Membrane electrodes selective to bupivacaine cations were developed and those with PVC-dibutylphthalate membrane containing sparingly soluble bupivacaine phosphotungstate appeared to be the most suitable. Inclusion complexation of bupivacaine cations with cyclodextrins was studied by potentiometric measurements of the free bupivacaine cation concentration in aqueous solutions of bupivacaine hydrochloride with cyclodextrin using the prepared electrodes. Native α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD), as well as their random-substituted derivatives hydroxypropyl-α-cyclodextrin (HP-α-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (M-β-CD), were chosen for the study. The measured potentiometric data processed both by a linear and nonlinear regression corroborated the formation of weak 1:1 bupivacaine cation-cyclodextrin complexes and the corresponding complexation constants K11 ∼50–155m−1 were evaluated by the non-linear least-squares method. The mutual order of K11 values, especially α-CD > β-CD, suggested that the bupivacaine butyl group was mainly responsible for the inclusion complexation; the highest K11 was exhibited by M-β-CD followed by α-CD. The observed complexation may substantially modify properties of bupivacaine hydrochloride dosage forms with sufficient concentration of cyclodextrin but bupivacaine cations are readily released from the weak cyclodextrin complexes by dilution.