Melnikova, Nina <br/><br/>
IMPROVEMENT OF BETULIN-3, 28-DIPHOSPHATE WATER- SOLUBILITY BY  COMPLEXATION WITH AMINES–MEGLUMINE AND XYMEDON  

 - Vol.11(5) 
 - M P  Innovare Academic Sciences Pvt Ltd  2019 
 - 48-55p. 
<br/><br/> Objective: <br/>To  study  betulin-3,28-diphosphate  (BDP)  water  solub<br/>ility  improved  by  forming  salt  complexes  with  hydro<br/>philic  amino  alcohols: <br/>meglumine as acidosis corrector and xymedon as the <br/>water-soluble antioxidant.<br/>Methods: <br/>We  used <br/>13<br/>C-, <br/>31<br/>P-NMR,  UV-spectroscopy  and  potentiometric  titration<br/>  to  study  the  BDP-amine  salt  complexes  formation  an<br/>d  their <br/>solubility using HPLC-analysis.<br/>Results: <br/>The participation of xymedon in the proton transfer<br/> reaction with BDP in aqueous solutions was confirm<br/>ed by the bathochromic shift of <br/>the carbonyl band from 299.1 nm to 304.2 nm, and by<br/> a hyperchromic effect (molar extinction ε from 850<br/>8 to 10 441 l·mol<br/>-1<br/>·cm<br/>-1<br/>) in UV-spectra. <br/>BDP complexation with meglumine was estimated by UV<br/>-spectral molar ratio method at 256 nm. Molar ratio<br/> of BDP-amine complexes (1:4) was <br/>proved by <br/>31<br/>P-NMR. The chemical shift of phosphorus at C-3 atom<br/> of BDP (δ =-0.58 ppm) changed to+3.39 ppm, and at <br/>C-28 atom (δ =+0.28 ppm)–<br/>to+4.60 ppm. BDP solubility increased 100-600 fold <br/>according to HPLC-analysis.<br/>Conclusion: <br/>BDP interaction with amine in an aqueous solution w<br/>as shown to proceed via a proton transfer due to re<br/>latively weak forces such as <br/>London  forces,  hydrogen  bonding,  electrostatic  and <br/>hydrophobic  interactions.  In  general,  the  formation<br/>  of  BDP  salt  complexes  with  amines  in <br/>solution determines BDP water solubility. Water-sol<br/>uble BDP enables to develop hydrophilic dosage form<br/>s.  
<br/><br/><label>Subjects--Topical Terms: </label><br/>PHARMACEUTICS