Background and Aims

Background and Aims

The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. Developing such co-formulation for a commercial product is very challenging due to different formulation conditions required to maintain the two peptides in stable form. The aim of the study reported here was to develop a stable co-formulation of PYY and liraglutide, a selected GLP-1.

Methods

Co-formulations were prepared in glass vials and the stability was assessed by reversed-phase chromatography (RP-HPLC) methods for the respective peptides and by a visual assessment compliant with the 2.9.20 EP Monograph. Stability was tested following storage at 30ºC.

Results

The initial screening demonstrated the incompatibility of PYY and liraglutide, and stability of the co-formulation in the composition of the marketed liraglutide product was found to be poor. Screening of various excipients and stabilising conditions resulted in identification of pharmaceutically acceptable compositions that enabled a stable liquid co-formulation of PYY and liraglutide

Fig. 1. Stability of PYY (left) and liraglutide (right) at 30ºC accelerated study in the Control formulation and a stabilising formulation developed in this study. The Control formulation failed the visual assessment at 4 weeks and 8 weeks; the stabilised formulation passed the visual assessment at all time-points.

Conclusions

The present study demonstrated the feasibility of developing a stable co-formulation of PYY and liraglutide. The stabilising compositions were based on excipients with history of use in injectable products for human use, which significantly de-risks further development plans.