Naslov
Phase solubility and H-NMR studies of bupivacaine hydrochloride complexation with different cyclodextrin derivates

Autori
Mario Jug, Natascia Mennini, Fabrizio Melani, Francesca Maestrelli, Paola Mura

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
II Congresso Nazionale Chimica e tedhnologia delle ciclodextrine, abstract book / Francesco Trotta - Asti, 2009, II-P1

Skup
II Congresso Nazionale Chimica e tedhnologia delle ciclodextrine

Mjesto i datum
Asti, Italija, 03.05.2009. - 05.05.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
bupivacain; beta-cyclodextrin derivates; solubility; 1H-NMR

Sažetak
Control of acute and chronic pain and regional anaesthesia upon surgery are topics of a great importance. This may be achieved by administration of local anesthetics, such as bupivacaine hydrochloride (BVP HCl), which is the most extensively used local anesthetic in surgical procedures worldwide. It has been demonstrated that inclusion complex formation of different local anesthetics has resulted in increased anesthetic effect in comparison to the plain drug accompanied with the reduced neurotoxicity of the drug [1]. Therefore, we studied the inclusion complexation of BVP HCl with different cyclodextrins in pH-controlled medium. To shed light on the possible role of the CD cavity size and of the presence and type of substituents in the inclusion complex formation, a list of cyclodextrins has been investigated, including alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), &#61472; gamma-cyclodextrin (gamma-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), randomly methylated-beta-cyclodextrin (RAMEB), sulphobutyl ether-beta-cyclodextrin sodium salt (SBE-beta-CD), soluble beta-cyclodextrin-epichlorohydrin polymer (EPI-beta-CD), hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD). Phase solubility studies indicated the formation of soluble inclusion complexes with all the tested CDs. In all cases, drug solubility linearly increased as a function of CD concentration, indicating the formation of equimolar drug/CD complexes. The cavity size of the host was not a selective factor for the effectiveness of native CDs, which all showed a similar limited complexing ability towards the drug. On the contrary, the presence of substituents increased the CD complexing power, and this effect depended upon the type of CD derivative. For the series of beta-CD derivatives, the stability constant value was growing in order HP-beta-CD< RAMEB< EPI-beta-CD< SBE-beta-CD. This indicated that the complexation of BVP HCL with tested CDs, beside the displacement of the energy-rich water molecules from the CD cavity, involved the interaction between the drug molecule and CD substituents, that additionally contributed to the overall complex stability. The complexation efficiency values for systems studied were also determined. Among tested CDs, EPI-beta-CD and SBE-beta-CD showed the highest complexing and solubilising power towards the drug, and thus these samples were further characterised by 1H NMR analysis. H-NMR studies were performed in D2O, using Watergate technique to suppress the signal of the residual water. In all cases an up field shift of H3 and H5 protons of CD and down field shift of the signals corresponding to distinct drug protons were observed, confirming the inclusion complex formation between BVP HCl and selected CDs. Based on NMR results, the structures of the inclusion complexes formed were proposed. 1. Dollo et al., Ann. Pharm. Fr., 58 (2000) 425

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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