Cumulative release kinetics of levothyroxine-Na pentahydrate from chitosan/arabinogalactane based pH sensitive hydrogel and it's toxicology

Abstract

In the study, a new hydrogel was synthesized by the freeze method of chitosan and arabinogalactan. The structure of the gel was characterized by SEM, XRD, TGA, and the interaction of macromolecules was determined. Swelling kinetics and degradation of hydrogel were studied. It was found that in the oxidizing medium, the degradation of the gel is 64% in 2 weeks, and in the elastase and PBS medium is about 19–22%. The hormone-substituted levothyroxine-Na pentahydrate was sorbed into the synthesized gel 50–200 μg depend on biopolymer mass ratio and studied for release in various media. It has been shown that the favourable yield (75–92%) and drug loading amount (40–220 μg) towards levothyroxine for all gel samples allows the use of chitosan based matrix for the delivery and controlled release of levothyroxine-Na. It was found that the controlled release of the levothyroxine-Na from the chitosan/arabinogalactan-based hydrogel to be consistent with the Hixson-Crowell, Korsmeyer-Peppas and Higuchi kinetic models, depending on the mole ratio of the polymers and the amount of immobilized sorbate molecules. Release of levothyroxine-Na with the highest values of R2 complies with the Higuchi (R2 = 0.968) in PBS for the CS/AG-11/LTH-Na-200 gel sample, with the Hixson-Crowell (R2 = 0.9156) and Korsmeyer-Peppas (R2 = 0.8594) kinetic models in the presence of elastase for the CS/AG-21-200, and best fitted to the Korsmeyer-Peppas (R2 > 0.9245) kinetic model for the CS/AG-51-200 gel in all media. In addition, a suspension of biopolymer hydrogel and its conjugate with levothyroxine in gastric medium was prepared and its acute and chronic toxicity was determined by injection (per os) method. It has been established that levothyroxine combined with a synthesized biopolymer belongs to the “practically non-toxic” group.