In Vitro andin vivo studies on the complexes of vinpocetine with hydroxypropyl-β-cyclodextrin
- 130 Downloads
The purpose of this study was to evaluate complexes of vinpocetine (VIN), a poorly water-soluble base type drug, with hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous environment and in solid state, with or without citric acid (CA) as an acidifier of the complexation medium. The apparent stability constant (Kc) calculated by phase solubility was 282 M-1 and the complexation in solution was structurally characterized by1H-NMR which showed VIN was likely to fit into the cyclodextrin cavity with its phenyl ring and ethyl ester bond. Solid complexes of VIN and HP-β-CD were prepared by kneading (KE), co-evaporating (CE) and freeze-drying (FD) methods. Physical mixtures were prepared for comparison. The study in the solid state included the differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and infrared absorption spectroscopy (IR). From these analyses, CE and FD products were found in amorphous state, allowing to the conclusion of strong evidences of inclusion complex formation. However, the dissolution test showed that only VIN/HP-β-CD+CA complexes by CE and FD method could provide satisfying dissolution behavior (rapid, complete and lasting) when compared to that of VIN/HP-β-CD complexes. Interestingly, the addition of CA in inclusion complexes could significantly decrease the amount of HP-β-CD needed to solubilize the same amount of VIN and thereby reducing the formulation bulk. Furthermore, in-vivo study revealed that the bioavailability of VIN after oral administration to rabbits (n=6) was significantly improved by VIN/HP-β-CD+CA inclusion complex.
Key wordsVinpocetine Hydroxypropyl-β-cyclodextrin Inclusion complexes Citric acid Improving dissolution rate Bioavailability
Unable to display preview. Download preview PDF.
- Amato, M. E., Lipkowitz, K. B., Lombardo, G. M., and Pappalardo, G. C., High-field NMR spectroscopic techniques combined with molecular dynamics simulations for the study of the inclusion complexes of α- and β-cyclodextrins with the cognition activator 3-phenoxypyridine sulphate (CI-844).Magn. Reson. Chem., 36, 693–705 (1998).CrossRefGoogle Scholar
- Brewster, M., Parental safety and application of 2-hydroxypropyl-β-cyclodextrin, In: Duchêne, D. (Ed.), NewTrends in Cyclodextrin and Derivatives, Editions de Santé, Paris, pp.313–351, (1991).Google Scholar
- Grandt, R., Beitinger, R., Schaltenbrand, R., and Braun, W., Vinpocetine pharmacokinetics in elderly subjects.Arzneimittelforschung./Drug Res., 39, 1599–1602 (1989).Google Scholar
- Higuchi, T. and Connors, K., Phase-solubility techniques,Adv. Anal. Chem. Instrum., 4, pp.117–212, (1965).Google Scholar
- Kata, M. and Gyorgy, E., Spruheinbettung von vinpocetine mit β-cyclodextrin.Phanvazie, 37, 386–387 (1982).Google Scholar
- Kata, M. and Lukács, M., Enhancement of solubility of vinpocetine base with γ-cyclodextrin.Phanvazie, 41, 151–152 (1986).Google Scholar