FORMULATION AND EVALUATION OF PARENTERAL IN-SITU FORMING BIODEGRADABLE IMPLANT FOR CONTROLLED RELEASE OF LEVOTHYROXINE SODIUM

Abstract

Objective: The objective of present research work is formulation and evaluation of parenteral in-situ forming biodegradable implant for controlled release of levothyroxine sodium. Material and Method: The present study used N-Methyl pyrrolidone (NMP) and triacetin as solvents and PLGA as a biodegradable polymer to manufacture two biodegradable polymeric drug delivery systems, in-situ forming implant (ISFI) and in-situ micro particles (ISM). Other evaluation tests, such as sterility, percent drug entrapment capacity, and so on, were also carried out. ISFI and ISM were tested for up to one month at three different temperatures (4ºC, 25ºC, and 40ºC). Result and Discussions: The drug release from both systems was compared. In batch F4, burst release was 10.72%, while in batch EP8, it was 8.16%. F4 was released 94.54% in roughly 30 days and EP8 was released 95.72%. The polymer content, type of solvent (hydrophilic or hydrophobic), and implant morphology all contributed to increased burst release in the ISFI formulation. Burst release was decreased using a combination of hydrophilic and hydrophobic solvents (NMP and Triacetin). When compared to other formulations, ISM had the lowest burst release. Both the ISFI and ISM formulations might deliver medications for up to 30 days. Both formulation show good drug entrapment efficiency F4 (87.74%) and EP8 (90.37%) respectively. Both formulations passed all their physicochemical proprieties included visual examination, pH, and injectability respectively. No visible growth of microorganisms was seen in growth media treated with both formulations after 30 days. The injection site (on the skin) and adjacent muscles showed no symptoms of irritation. It was confirmed when the results were compared to those of the control group. There was no hyperemia, discoloration, or necrosis at the site and no sign of irritation by both formulations. In the case of ISM (EP8), drug release follows zero order kinetics with an R2 value of 0.9814 and ISFI (F4) follows Korsmeyer peppas and both transport drug through Fickian diffusion mechanism. Both formulations were found to, be stable. Hence, Long-acting Levothyroxine sodium formulations (ISFI & ISM) may be a superior option for hypothyroidism treatment.