Effects of divalent cations on drug encapsulation efficiency of deacylated gellan gum

The objective of this research was to evaluate the effects of various divalent cations on the encapsulation efficiency of gellan gum and to probe the underlying mechanisms responsible for drug-loading efficiency. Spherical beads containing azathioprine were prepared from deacetylated gellan gum by ionotropic gelation method. One molar solution of various divalent chlorides (MgCl(2), BaCl(2), CaCl(2), CuCl(2) and ZnCl(2)) and two additional concentrations of CaCl(2) (2.5 M and 5.0 M) were used as ionotropic media. Drug solubility was also determined in these ionotropic media and statistically evaluated using ANOVA. Solubility in various divalent chloride solutions (1.0 M) suggests that azathioprine forms complex with Ca(2+), Zn(2+) and Cu(2+), while there might be a formation of poorly water-soluble chelates with Mg(2+) and Ba(2+) as solubility in these media were less than in deionized water. The encapsulation efficiency of gellan gum was much higher in the presence of transition elements (Cu(2+) and Zn(2+)) when compared to alkaline earth metal ions (Ca(2+), Mg(2+) and Ba(2+)). Higher concentrations of Ca(2+) decreased the encapsulation efficiency of gellan gum in a nearly proportional manner. The correlation between encapsulation efficiency and pH of the ionotropic media was negative and significant (r=-0.9574, p<0.05), although the solubility of azathioprine seems to be independent of the pH of the ionotropic medium. Overall, the results suggest that drug encapsulation efficiency of deacetylated gellan gum is largely affected by the concentration and nature of various divalent cations (e.g. atomic number, valency or electro-positivity, co-ordination property, etc.) and pH of the ionotropic medium.