Effect of external factors on the curcumin/2-hydroxypropyl-β-cyclodextrin: in vitro and in vivo study

Abstract

The effect of 2-hydroxypropyl-b-cyclodextrin (HPbCD) on solubility, stability and oral bioavailability of curcumin by external factors adjustment, was investigated with an aim of a simple, stable and effective formulation. The phase solubility studies showed the solubility of curcumin increased slightly with increasing pH. However, the apparent stability constant (K S ) were found to decrease with increasing pH from 1.29 9 10 4 M -1 at pH 3.0 to 5.22 9 10 3 M -1 at pH 7.0. The thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. Interestingly, it could be concluded that the degrees of curcumin stability improved by HPbCD grew with increasing drugcyclodextrin binding ability. Furthermore, in vivo study not only revealed that the bioavailability of curcumin after oral administration to rats was significantly improved by curcumin/HPbCD inclusion complex, but also showed more dramatic changes in the plasma concentration-time curve (1752.76-866.70 ng mL -1 h) and the peak plasma concentration (370.10-178.11 ng mL -1 ) of drug by formation of complexes in pH 3-7 solution.Keywords Cyclodextrin Á Curcumin Á Phase solubility Á Stability Á Pharmacokinetics Abbreviations CD Cyclodextrin HPbCD 2-Hydroxypropyl-b-cyclodextrin HPLC High performance liquid chromatography S 0 Solubility in a medium in the absence of CD K S Apparent stability constant for the drug-CD interaction [C 0 ] The initial concentration of drug [C t ] The time-dependent concentration of drug DH Values of enthalpy change DS Values of entropy change DG Variation of Gibbs free energy kObserved first-order rate constant of drug k 0 Observed first-order rate constant of drug in the absence of CD k C Observed first-order rate constant for the inclusion complex E a Activation energy (the amount of energy needed to initiate a chemical process, most often a reaction) R.S.D.Relative standard deviation C max Maximum plasma concentration T max Time required to reach C max AUC Total area under the plasma concentrationtime AUC (0-24) Total area under the plasma concentrationtime curve from 0 to 24 h AUC (0-?) Total area under the plasma concentrationtime curve from time zero to infinity

Dual drug-loaded halloysite hybrid-based glycocluster for sustained release of hydrophobic molecules

“…45 These results demonstrated that Sil and Cur in the 1/Sil/Cur displayed a sustained and long-term release prole, with a total amount of Sil and Cur released being about 23% and 5%, respectively, within 60 min and 65% and 5% respectively, aer 400 min in acidic solution. On the contrary, 10% of both molecules within 60 min and 13% and 12% of Sil and Cur respectively in physiological condition were released.…”

The soluble curcumin derivative NDS27 inhibits superoxide anion production by neutrophils and acts as substrate and reversible inhibitor of myeloperoxidase

“…Curcumin lysinate might interact with HPβCD in two ways. Either in a stoichiometry of curcumin:cyclodextrin of 1:1 having one aromatic ring included in the cyclodextrin cavity or a stoichiometry of 1:2 having each of the two aromatic moieties included in two cyclodextrin cavity [41,42]. According to Shitiyakov et al [43], a 1:1 binding isotherm for the curcumin:cyclodextrin complex seems more likely, although some 1:2 complexation was suspected between curcumin and HPβCD [44].…”

Nutritional value, phytochemical composition, and biological activities of edibleCurcumaspecies: A review

“…[94] In addition, several attempts have been made to encapsulate curcumin by chemical/physicochemical and physical-mechanical methods including nanoparticles, liposomes, micelles, and phospholipid complexes to enhance its bioavailability and bioaccessibility. [95][96][97][98][99][100][101][102] …”