Characterization Of Lidocaine:hydroxypropyl-β-cyclodextrin Inclusion Complex

An inclusion complex was prepared between the local anesthetic lidocaine (LDC) and hydroxypropyl-β-CD (HP-β-CD). The complex was characterized by thermal analysis (differential scanning calorimetry, DSC), UV absorption and high-pressure liquid chromatography (HPLC). DSC results were indicative of complexation, due to the loss of the characteristic endothermic peak of LDC (77°C). Phase-solubility diagrams allowed the determination of the association constant between LDC and HP-β-CD (35.7 ± 4.7 M -1). The rate of LDC release decreased after complexation and thermodynamic parameters from the HPLC studies (ΔG° = -2.65 kJ/mol) revealed that a stable complex was formed. © 2007 Springer Science+Business Media, Inc.5701/04/15313316de Jong, R.H., (1994) Local anesthetics, , C. C. Thomas, SpringfieldCovino, B.G., Vassalo, H.G., (1976) Local anesthetics: Mechanisms of action and clinical use, , Grune and Stratton, New YorkStanley, T.H., New routes of administration and new delivery systems of anesthetics (1988) Anaesthesiology, 38, pp. 665-668Duchene, D., (1987) Cyclodextrins and their industrial uses. Editions de Sant, , ParisBrewster, M.E., Simpkins, J.W., Hora, M.S., Stern, W.C., Bodor, N., The potential use of cyclodextrins in parenteral formulations (1989) J. Parenter. Sci. Technol, 43, pp. 231-240Szejtli, J., Introduction and general overview of cyclodextrin chemistry (1998) Chem. Rev, 98, pp. 1743-1754Bekers, O., Uijtendaal, E.V., Beijnen, J.H., Bult, A., Underberg, W.J.M., Cyclodextrins in the pharmaceutical field (1991) Drug Dev. Ind. Pharm, 17, pp. 1503-1549Sinesterra, R.D., Najjar, R., Conde da Silva, A.L., Alves, O.L., Santos, P.S., de Alves Carvalho, F.C., The inclusion of rhodium(II) α- methylcinnamate in β-cyclodextrin (1995) J. Incl. Phenom, 22, pp. 91-98Pralhad, T., Rajendrakumar, K., Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis (2004) J. Pharm. Biomed. Anal, 34, pp. 333-339Higuchi, T., Connors, K.A., Phase-solubility techniques (1965) Adv. Anal. Chem. Inst, 4, pp. 117-212Fraceto, L.F., Pinto, L.M.A., Franzoni, L., Braga, A.A., Spisni, A., Schreier, S., de Paula, E., Spectroscopic evidence for a preferential location of lidocaine inside phospholipid bilayers (2002) Biophys. Chem, 99, pp. 229-243Tommasini, S., Raneri, D., Ficarra, R., Calabró, M.L., Stancanelli, R., Ficarra, P., Improvement in solubility and dissolution rate of flavonoids by complexation with beta-cyclodextrin (2004) J. Pharm. Biomed. Anal, 35, pp. 379-387Loukas, Y.L., Vraka, V., Gregoriadis, G., Novel non-acidic formulations of haloperidol complexed with beta-cyclodextrin derivatives (1997) J. Pharm. Biom. Anal, 16, pp. 263-268Grant, G.J., Bansinath, M., Liposomal delivery systems for local anesthetics (2001) Reg. Anesth. Pain. Med, 26, pp. 61-63Ismaili, L., André, C., Nicod, L., Mozer, J.L., Millet, J., Refouvelet, B., Makki, S., Guillaume, Y.C., Chromatographic determination of the association constants between Psorasolen derivatives and modified β-cyclodextrin: Effect of sucrose as a co-enhancer association agent (2003) J. Liq. Chrom. & Relat. Technol, 26, pp. 871-882Ravelet, C., Ravel, A., Grosset, C., Villet, A., Geze, A., Wouessidjewe, D., Peyrin, E., Stoichiometry and formation constants of six PAHs with γ-Ciclodextrin, determined by HPLC using a cyano stacionary phase (2002) J. Liq. Chrom. & Rel. Technol, 25, pp. 421-432Rozou, S., Voulgari, A., Antoniadou-Vyza, E., The effect of pH dependent molecular conformation and dimerization phenomena of piroxicam on the drug:cyclodextrin complex stoichiometry and its chromatographic behaviour. A new specific HPLC method for piroxicam:cyclodextrin formulations (2004) Eur. J. Pharm. Sci, 21, pp. 661-669Blais, J., Prognon, P., Mahuzier, G., Vigny, P.J., Relative affinity of 5-methoxypsoralen and 8-methoxypsoralen towards β-cyclodextrin: A fluorescence, circular dichroism and chromatographic study (1998) Photochem. Photobiol. B, 2, p. 455Morin, N., Guillaume, Y.C., Peyrin, E., Rouland, J.C., Peculiarities of an imidazole derivative retention mechanism in reversed-phase liquid chromatography: β-cyclodextrin concentration and temperature considerations (1998) J. Chromatogr. A, 808, pp. 51-60Stalcup, A.M., Chang, S.S., Armstrong, D.W., Pitha, J.J., (S)-2-Hydroxyprophyl-β-cyclodextrin, a new chiral stationary phase for reversed-phase liquid chromatography (1990) J. Chromatogr. A, 513, pp. 181-19