Abstract
The objective of this research work was to develop and evaluate novel alendronate-chitosan (AL-CH) complex for the enhancement of bioavailability of alendronate. AL-CH complex was prepared by phosphoramide coupling reaction between thionyl chloride activated hydroxyl groups of alendronate and amino group of chitosan. The complex formation was characterized by FTIR, XRD and zeta potential measurements. Drug release and in vivo pharmacokinetics of the developed complex was evaluated. Phosphoramide bond formation between alendronate and chitosan was confirmed by FTIR. AL-CH complex was found to be amorphous with zeta potential of + 16.4 mV, in contrast to alendronate, which was crystalline with zeta potential of -2.3 MV. Drug release studies showed that alendronate was released in a sustained pattern from complex over a period of 8 hrs. Compared to AL solution, AL-CH complex demonstrated significantly higher (p<0.001) intestinal permeability as determined by non-everted rat gut technique. The in vivo study in rats demonstrated similar to 8-fold higher bone deposition of AL following oral administration of AL-CH complex compared to AL solution. In conclusion, AL-CH complex is a promising formulation for the delivery of alendronate sodium enhancing its bone deposition.