Naslov
Study of zaleplon/cyclodextrin complexation by 1H-NMR spectroscopy

Autori
Jug, Mario ; Jablan, Jasna

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

Izvornik
Bio-NMR and EAST-NMR Annual User Meeting / Sklenar, Vladimir - Brno : NCBR and CEITEC, Masaryk University, Brno, Czech Republic, 2011, 38-38

Skup
First Bio-NMR and second EAST-NMR Annual User Meeting

Mjesto i datum
Brno, Češka Republika, 24.01.2011. - 27.01.2011

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
1H-NMR; DOSY; ROESY; zaleplon; cyclodextrin

Sažetak
Cyclodextrins (CDs) are a group of structurally related cyclic oligosaccharides derived from bacterial starch degradation. The ground for their popularity from a pharmaceutical point of view is in their ability to favourably modify undesired biopharmaceutical properties of the drug, such low chemical stability and limited aqueous solubility, by the inclusion complex formation. Numerous CD derivatives has been synthesized in order to extend complexing and solubilizing properties of naturally occurring CDs. Due to their bioavailability and lack of oral toxicity, CDs are used as carriers in order to improve bioavailability of drugs with limited aqueous solubility or to achieve controlled drug release. Zaleplon (ZAL) is a hypnotic drug indicated for a short term therapy of insomnia. Due to low solubility in water, the oral bioavailability of the ZAL is only 30% of applied dose. In order to improve aqueous solubility and consequently increase oral bioavailability of the drug, the interaction of ZAL with natural β-CD and its randomly methylated derivative (RAMEB) was studied. 1H-NMR spectroscopy was used to confirm the actual inclusion complex formation and to put some insight into host-guest binding mode. One dimensional 1H-NMR showed that in the presence of ZAL, H3 and H5 proton, which are lining the interior of the cavity of βCD and H6 proton, which is located at the narrower end of the βCD torus, experienced a strong shielding effect, clearly confirming the actual inclusion complex formation. In the same time, the majority of ZAL protons showed a down-field shift in their resonances, due to deshielding effects caused by van der Waals interaction between the drug and carbohydrate ring upon complexation. In case of RAMEB, deep penetration of ZAL into central cavity of CD was also evidenced. Further evidence for the inclusion complex formation between ZAL and CDs was obtained by DOSY spectroscopy, while ROESY spectra allowed determination of ZAL/CD binding modes.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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