Optimization and in Vitro Evaluation of Injectable Sustained-Release of Levothyroxine Using PLGA-PEG-PLGA

Purpose In situ-forming gels (semi-solid state) (ISFGs) are widely used as sustained drug delivery, but they show a high burst release as well. The purpose of the current study is to make triblock that can make a quick gel on injection with a minimum burst release. Methods In this study, to control the release of levothyroxine from ISFG, PLGA-PEG-PLGA (triblock) polymer was used. The melting method was employed to synthesize the triblock via ring-opening polymerization (ROP). Different weight percentages of triblock in the formulation were investigated to reach the minimum initial burst release of levothyroxine from ISFGs.Furthermore, the results of the in-situ forming implant (solid-state) (ISFI) of levothyroxine prepared from PLGA 504 H polymers were compared with ISFG. Results The melting method employed in this study showed a successful ROP of the triblock. As the % triblock concentration was increased from 30 to 50%, the initial burst release decreased significantly. The initial burst release levothyroxine from ISFG (6.52 +/- 0.30%) was much lower than the amount of levothyroxine released from ISFI (14.15 +/- 0.79%). No cytotoxicity was observed for the sustained-release formulation containing ISFG 50% according to the MTT assay. Conclusion The results indicated that this formulation was safe to be administered subcutaneously. As the synthesized triblock has thermosensitive properties, and also has the hydrogen bonding between the N-methyl pyrrolidone molecules and PEG, therefore, these properties make ISFG formulation to have a smaller initial burst release compared to ISFI formulation.

Automated summary

In this study, a triblock polymer was synthesized using the melting method for controlled release of levothyroxine from in situ-forming gels. Increasing the concentration of triblock in the formulation significantly reduced the initial burst release of levothyroxine. The triblock showed thermosensitive properties and hydrogen bonding, leading to a smaller initial burst release compared to in situ forming implants.