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The drug Liraglutide is an acylated analogue of glucagon-like peptide-1 (GLP-1) which is indicated for the treatment of type 2 diabetes mellitus and chronic obesity. Stability testing of biopharmaceuticals is an essential part of their quality control, aimed at revealing possible degradation pathways and identification of potential degradation products. Up to now, no information on the Liraglutide behaviour in formulation medium under stress conditions has been provided. In the present study, the original innovator and an analogue product of Liraglutide were subjected to stress by exposing to various temperature, pH and oxidation conditions to generate possible degradation products and aggregation. Liquid chromatography-mass spectrometry was used to determine impurity profiles and identify degradation products of stressed drug samples from different suppliers. Results showed that Liraglutide products exhibit high stability at room temperature. Exposure to high pH resulted in the formation of aggregates and chemical modifications, including oxidation, while exposure to low pH caused peptide precipitation. Liraglutide formulations showed slight susceptibility to oxidation on tryptophan residue. Overall, no significant differences were observed between the originator and the analogue of Liraglutide. Both exhibited similar behaviour in their impurity profiles during forced degradation. The approach used in this study offers potential benefits for industrial purposes in formulation development and product characterization. [ABSTRACT FROM AUTHOR]

Biodegradable polyesters are widely employed in the development of controlled release systems for peptide drugs. However, one of the challenges in developing a polyester-based delivery system for peptides is the acylation reaction between peptides and polymers. Peptide acylation is an important factor that affects formulation stability and can occur during storage, in vitro release, and after drug administration. This review focuses on the mechanisms and parameters that influence the rate of peptide acylation within polyesters. Furthermore, it discusses reported strategies to minimize the acylation reaction. [ABSTRACT FROM AUTHOR]

Purpose: Polyesters with hydrophilic domains, i.e., poly( d,l-lactic- co-glycolic- co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly( l-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic matrices. Our purpose is to assess the extent and sites of acylation of octreotide loaded in microspheres using tandem mass spectrometry analysis. Methods: Octreotide loaded microspheres were prepared by a double emulsion solvent evaporation technique. Release profiles of octreotide from hydrophilic microspheres were compared with that of PLGA microspheres. To scrutinize the structural information and localize the actual modification site(s) of octreotide, liquid chromatography ion-trap mass spectrometry (LC-ITMS) was performed on the acylated adducts. Results: Hydrophilic microspheres showed less acylated adducts in comparison with PLGA microspheres. LC-MS/MS showed that besides the N-terminus and primary amine of lysine, the primary hydroxyl of the end group of octreotide was also subjected to acylation. Nucleophilic attack of the peptide can also occur to the carbamate bond presented in (PC-PEG-PC)-(PL) since 1,4-butanediisocyanate was used as the chain extender. Conclusions: Hydrophilic polyesters are promising systems for controlled release of peptide because substantially less acylation occurs in microspheres based on these polymers. LC-ITMS provided detailed structural information of octreotide modifications via mass analysis of ion fragments. [ABSTRACT FROM AUTHOR]