TY - JOUR

T1 - Supramolecular Complex of Ibuprofen with Larch Polysaccharide Arabinogalactan

T2 - Studies on Bioavailability and Pharmacokinetics

AU - Khvostov, Mikhail V.

AU - Borisov, Sergey A.

AU - Tolstikova, Tatjana G.

AU - Dushkin, Alexander V.

AU - Tsyrenova, Biligma D.

AU - Chistyachenko, Yulia S.

AU - Polyakov, Nikolay E.

AU - Dultseva, Galina G.

AU - Onischuk, Andrey A.

AU - An’kov, Sergey V.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background and Objectives: In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen’s bioavailability and decrease its effective dose after oral administration. Methods: The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction. Results: It was found that ibuprofen’s effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats’ plasma: Cmax of IBU at doses of 20 and 40 mg/kg was found as 0.088 and 0.132 μg/ml, whereas Cmax of IBU in the complex form was 0.103 and 0.160 μg/ml, respectively. Conclusions: Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.

AB - Background and Objectives: In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen’s bioavailability and decrease its effective dose after oral administration. Methods: The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction. Results: It was found that ibuprofen’s effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats’ plasma: Cmax of IBU at doses of 20 and 40 mg/kg was found as 0.088 and 0.132 μg/ml, whereas Cmax of IBU in the complex form was 0.103 and 0.160 μg/ml, respectively. Conclusions: Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.

KW - PERFORMANCE LIQUID-CHROMATOGRAPHY

KW - DRUG-DELIVERY-SYSTEMS

KW - ULTRAVIOLET DETECTION

KW - OLIGOSACCHARIDES

KW - SEPARATION

KW - PLASMA

UR - http://www.scopus.com/inward/record.url?scp=84976407537&partnerID=8YFLogxK

U2 - 10.1007/s13318-016-0357-y

DO - 10.1007/s13318-016-0357-y

M3 - Article

C2 - 27351190

AN - SCOPUS:84976407537

VL - 42

SP - 431

EP - 440

JO - European Journal of Drug Metabolism and Pharmacokinetics

JF - European Journal of Drug Metabolism and Pharmacokinetics

SN - 0378-7966

IS - 3

ER -