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.
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.
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.
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.