Objective:
To study betulin-3,28-diphosphate (BDP) water solub
ility improved by forming salt complexes with hydro
philic amino alcohols:
meglumine as acidosis corrector and xymedon as the
water-soluble antioxidant.
Methods:
We used
13
C-,
31
P-NMR, UV-spectroscopy and potentiometric titration
to study the BDP-amine salt complexes formation an
d their
solubility using HPLC-analysis.
Results:
The participation of xymedon in the proton transfer
reaction with BDP in aqueous solutions was confirm
ed by the bathochromic shift of
the carbonyl band from 299.1 nm to 304.2 nm, and by
a hyperchromic effect (molar extinction ε from 850
8 to 10 441 l·mol
-1
·cm
-1
) in UV-spectra.
BDP complexation with meglumine was estimated by UV
-spectral molar ratio method at 256 nm. Molar ratio
of BDP-amine complexes (1:4) was
proved by
31
P-NMR. The chemical shift of phosphorus at C-3 atom
of BDP (δ =-0.58 ppm) changed to+3.39 ppm, and at
C-28 atom (δ =+0.28 ppm)–
to+4.60 ppm. BDP solubility increased 100-600 fold
according to HPLC-analysis.
Conclusion:
BDP interaction with amine in an aqueous solution w
as shown to proceed via a proton transfer due to re
latively weak forces such as
London forces, hydrogen bonding, electrostatic and
hydrophobic interactions. In general, the formation
of BDP salt complexes with amines in
solution determines BDP water solubility. Water-sol
uble BDP enables to develop hydrophilic dosage form
s.