Preparation and in vitro evaluation of injectable formulations of levothyroxine sodium using in situ forming hydrogel temperature-responsive systems based on PLA-PEG-PLA and PLGA-PEG-PLGA triblock copolymers

Abstract

Objective(s): Recently, great attention has been paid to developing new drug delivery systems to manage the rate, time, and site of drug release. We aimed to design a novel drug delivery system to support targeted and gradual delivery of levothyroxine sodium.Materials and Methods: The triblock copolymers of PLA-PEG-PLA and PLGA-PEG-PLGA were constructed using the ring-opening copolymerization method and then purified and characterized by 1H-NMR, DSC, and GPC techniques. The phase transition temperature of the polymers was determined, and levothyroxine sodium stability was investigated in a phosphate-based buffer (pH 7.4). In vitro drug release into the PBS was measured at different concentrations of the triblocks for one month. Results: The results of NMR and GPC showed successful fabrication of the copolymers with low molecular weight dispersion and Tg points of -8.19 °C and -5.19 °C for PLA-PEG-PLA and PLGA-PEG-PLGA, respectively. Stability tests showed that during one month, most of the triblocks’ masses degraded at 37 °C while levothyroxine sodium remained stable. Initial burst release of the drug in both copolymers is inversely correlated with the concentration of the polymer. Evaluation of drug release for 35 days showed that PLA-PEG-PLA had a slower drug release rate than PLGA-PEG-PLGA.Conclusion: Considering the low initial burst release, as well as continuous and long-term release kinetics of PLA-PEG-PLA and PLGA-PEG-PLGA copolymers, they can be used to gradually deliver levothyroxine sodium, obviating the need for frequent administrations and concerns over drug-food interactions.

Keywords

• in situ forming hydrogel- gelling
• levothyroxine sodium
• smart hydrogels
• temperature-responsive- systems
• triblock copolymer