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

Abstract

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 (MgCl2, BaCl2, CaCl2, CuCl2 and ZnCl2) and two additional concentrations of CaCl2 (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 Ca2+, Zn2+ and Cu2+, while there might be a formation of poorly water-soluble chelates with Mg2+ and Ba2+ 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 (Cu2+ and Zn2+) when compared to alkaline earth metal ions (Ca2+, Mg2+ and Ba2+). Higher concentrations of Ca2+ 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 electropositivity, co-ordination property, etc.) and pH of the ionotropic medium.