Effects of Surface Morphology and Type of Cross-Linking of Chitosan-Pectin Microspheres on Their Degree of Swelling and Favipiravir Release Behavior

The cross-linked microspheres were prepared and loaded with Favipiravir SARS-CoV-2 antiviral drug, by copolymerization of chitosan (CS) with a polysaccharide extracted from fresh pomegranate peels. Moreover, glutaraldehyde (Glu) has been used as a chemical cross-linker and sodium hexametaphosphate (SHMP) as a physical cross-linker. The extracted polysaccharide was analyzed, and different techniques have been used. The analyses lead to the conclusion that it is pectin. The surface morphology of the prepared microspheres was studied using a scanning electron microscope, where the size and shape factor (S) of the Glu microspheres showed high values (74.27 μm) and (0.852), respectively, meaning their surfaces tend to be rough, whereas the SHMP microspheres showed a smaller size particle (20.47 μm) and a smaller shape factor (0.748), which gives an indication that the SHMP microspheres have smooth surfaces. The swelling studies have shown that Glu microspheres have a higher degree of swelling, which means SHMP microspheres are more compact. The prepared microspheres have shown a higher loading percentage of Favipiravir antiviral drug in SHMP microspheres (37% w/w) in comparison with Glu microspheres (35% w/w), where the electrostatic interaction between the Favipiravir ions and SHMP anions helps for more loading. The microspheres prepared under different types of cross-linking have shown initial burst release of Favipiravir, followed by a step of controlled release for a certain period of time, whose period depends on the pH of the release medium. Both Glu and SHMP cross-linked microspheres have shown high controlled release times in buffered release solutions at pH = 7.4 and for shorter periods at pH = 1.3 and pH = 9.4, which may be related to the type of electrostatic interactions between drug and polymer systems and their reactions with release solution ions.