Monitoring the formation of the cinnarizine: hydroxypropyl-β-cyclodextrin inclusion complex in solution by spectroscopy nmr

Kragić, Gordan; Sakoman, Franjo; Čikoš, Ana; Galić, Nives (2025) Monitoring the formation of the cinnarizine: hydroxypropyl-β-cyclodextrin inclusion complex in solution by spectroscopy nmr. In: Stantić, Vedrana; Štorga, Lara; Borovec, Jakov, (eds.) 10th Symposium of Chemistry Students : Book of abstracts. Zagreb, Croatia, University of Zagreb Faculty of Science, Zagreb, Croatia, p. 78 .

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Abstract

Cinnarizine, one of piperazine derivatives with multiple pharmacological activities, was limited in its clinical application due to poor solubility in aqueous media. One of the approaches to improve its solubility was the formation of inclusion complexes with cyclodextrins. Specifically, the possibility of cinnarizine complexation with hydroxypropyl- β-cyclodextrin (HP-β-CD) was examined using nuclear magnetic resonance (NMR) spectroscopy. The interaction between the two molecules was assessed by monitoring chemical shift changes during titration of cinnarizine with HP-β-CD solutions, and the results indicated inclusion of the cinnarizine molecule into the cavity of HP-β-CD, with the orientation being assumed only on the basis of molecular size. Titration of cinnarizine with HP-β-CD solutions was carried out at two different DCl concentrations (c = 1.0 mol dm⁻3 and c = 0.01 mol dm⁻3) to examine the influence of medium acidity on complexation. At the higher acid concentration, no significant chemical shift changes were observed, suggesting that the predominantly diprotonated form of cinnarizine was not stable inside the cyclodextrin cavity. In contrast, at lower acidity, where both mono- and diprotonated forms were present, clear changes in the 1H NMR spectra indicated inclusion complex formation, particularly evident for H-7, whose chemical shift systematically changed upon HP-β-CD addition, and for protons H-9,13,15,19, which shifted upfield. Although the observed patterns resembled those with β-cyclodextrin, detailed analysis of cyclodextrin protons was hindered by overlap and broadening of HP-β-CD signals in the 3–4 ppm region. Changes in the appearance of these signals further supported the conclusion of complex formation. The shift of the CIN H- 7 signal did not level off at a cinnarizine:HP-β-CD ratio of 1:1 but continued up to 1:2, suggesting the possible involvement of one cinnarizine molecule in two HP-β-CD cavities. However, due to the limitations of the 1H NMR technique, an unambiguous conclusion regarding the inclusion mode could not be drawn without additional complementary methods.

Item Type:	Conference or workshop item published in conference proceedings (UNSPECIFIED)
Uncontrolled Keywords:	NMR spectroscopy; cinnarizine; hydroxypropyl-β-cyclodextrin; inclusion complex
Subjects:	NATURAL SCIENCES > Chemistry > Analytic Chemistry
Divisions:	NMR Center
Projects:	Project title Project leader Project code Project type Priprava, karakterizacija i biokompatibilnost novih supramolekulskih kompleksa lijek/ciklodekstrin i lijek/dekstrinske nanospužve s poboljšanim svojstvima Nives Galić IP-2022-10-6033 HrZZ
Depositing User:	Franjo Sakoman
Date Deposited:	22 Jan 2026 09:38
URI:	http://fulir.irb.hr/id/eprint/10907

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