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

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Abstract

The effect of 2-hydroxypropyl-β-cyclodextrin (HPβCD) 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 × 104 M−1 at pH 3.0 to 5.22 × 103 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 HPβCD grew with increasing drug–cyclodextrin binding ability. Furthermore, in vivo study not only revealed that the bioavailability of curcumin after oral administration to rats was significantly improved by curcumin/HPβCD 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.

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Abbreviations

CD:

Cyclodextrin

HPβCD:

2-Hydroxypropyl-β-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

ΔH :

Values of enthalpy change

ΔS :

Values of entropy change

ΔG :

Variation of Gibbs free energy

k :

Observed 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 concentration–time

AUC(0–24) :

Total area under the plasma concentration–time curve from 0 to 24 h

AUC(0–∞) :

Total area under the plasma concentration–time curve from time zero to infinity

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Acknowledgment

This study was supported by Tianjin Science and Technology Development Fund for Colleges and Universities (20090223).

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Authors and Affiliations

  1. Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, China

    Hui-Zi Ouyang, Ling Fang, Xiao-Liang Ren & Ai-Di Qi

  2. Key Laboratory of Traditional Chinese Medicine Pharmacology, Nankai District, Tianjin, 300193, China

    Lei Zhang

  3. Key Laboratory of Traditional Chinese Medicinal Chemistry and Analytical Chemistry of Tianjin, Nankai District, Tianjin, 300193, China

    Hui-Zi Ouyang, Lin Zhu & Jun He

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  1. Hui-Zi Ouyang
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Ouyang, HZ., Fang, L., Zhu, L. et al. Effect of external factors on the curcumin/2-hydroxypropyl-β-cyclodextrin: in vitro and in vivo study. J Incl Phenom Macrocycl Chem 73, 423–433 (2012). https://doi.org/10.1007/s10847-011-0080-x

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