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 alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD), as well as their random-substituted derivatives hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and methyl-beta-cyclodextrin (M-beta-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 K(11) approximately 50-155 M(-1) were evaluated by the non-linear least-squares method. The mutual order of K(11) values, especially alpha-CD > beta-CD, suggested that the bupivacaine butyl group was mainly responsible for the inclusion complexation; the highest K(11) was exhibited by M-beta-CD followed by alpha-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.

Micellization of the local anesthetic drug carbisocaine hydrochloride (BHCl) was studied by potentiometry with both cation- and anion-selective membrane electrodes in aqueous solution at 25 °C. The found critical micelle concentration 0.022 mol dm-3 and the concentration course of the free carbisocaine cation and chloride counterion in the micellar solution corresponded to the characteristic of cationic surfactants. In a more dilute aqueous solution, below critical micelle concentration, the complexation of carbisocaine cation BH+ with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and its random substituted methyl (M-β-CD) and hydroxypropyl (HP-β-CD) derivatives was followed using the prepared cation-selective electrodes. The potentiometric data corroborated formation of the carbisocaine-cyclodextrin complexes (BH+)CD (1 : 1) with all the cyclodextrins and the respective complexation constants K11 were estimated using a modified Scatchard method. Slight deviations from 1 : 1 plots were marginally observed with α-CD and HP-β-CD. Bigger K11 value of the complexation with α-CD in comparison with β-CD indicated inclusion of the carbisocaine C7 alkyl chain into the cyclodextrin cavity and the role of the hydrophobic interaction in complexation with β-CDs was emphasized by the increasing magnitude of K11 in the order of HP-β-CD < β-CD < M-β-CD.

Inclusion complexation of an antimicrobial quaternary ammonium salt, carbethopendecinium bromide (SBr, Septonex), with five cyclodextrins was investigated potentiometrically using the prepared membrane electrodes selective to the surface-active carbethopendecinium cations (S+). Relatively strong complexation of the S+ cations with native α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and their random-substituted derivatives, namely hydroxypropyl-α-cyclodextrin (HP-α-CD), methyl-β-cyclodextrin (M-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD), was evidenced in dilute aqueous solution. In the region where the potentiometrically determined concentration of the free S+ cations remained lower than the critical micelle concentration (cmc) of SBr by a factor of ca ten, formation of the 1:1 complexes with the complexation constants K11 ≈ 104-105 was evaluated by two respective methods, based on a modified linear and a non-linear regression. Deviations from the 1:1 complexation were observed when concentration of the free S+ cations approached cmc of SBr more closely and also in solutions with large excess of α-CD. Comparison of K11 values corroborated the inclusion of the n-C14H29 alkyl chain of the carbethopendecinium cation as the mechanism of its complexation with cyclodextrins. The well-soluble native α-CD with good complex-forming capability towards S+ cations may be especially suitable for possible blocking the undesirable residues of carbethopendecinium bromide.

No abstract

The critical micellar concentrations (cmc) of the title cationic surfactants were measured in aqueous solutions at 25 °C in the presence of KBr, KF, KCl, KI, KSCN, KNO3, KAc and HCOOK. The conductometric and, in part, potentiometric methods employing ion selective electrodes were used. For 1-cetylpyridinium bromide in the absence of any of the electrolytes, the decreasing temperature dependence of cmc was measured conductometrically over the region of 12 - 40 °C and the association degree of the micelles with Br- anions was calculated. The decrease in cmc of the two surfactants due to the presence of electrolytes (in concentrations up to tenfold cmc) was expressed by means of a semiempirical equation. There are indications that I- and SCN- anions enter into specific interactions with micelles.