Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study.

Autor:	Sheikh AR; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Vitore JG; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Bhalekar VS; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Jain S; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Kukreja D; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Giri T; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India., Sharma N; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India. Electronic address: nitish.sharma@niperahm.res.in., Benival D; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India. Electronic address: derajram@niperahm.res.in., Shah RP; Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), India. Electronic address: ravi.shah@niperahm.ac.in.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Nov; Vol. 113 (11), pp. 3246-3254. Date of Electronic Publication: 2024 Aug 22.
DOI:	10.1016/j.xphs.2024.08.007
Abstrakt:	The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc. The peptide contains various amino acids such as histidine, lysine, and arginine having free amine groups. These amine groups act as strong nucleophile and can increase the reactivity of peptides. PLGA is the most widely used biodegradable polymer in sustained-release formulations. The hydrolysis of PLGA generates glycolic acid and lactic acid impurities, which can form the interaction product with the amines of peptides. During the formulation development of Liraglutide, we have found few interaction products. The systematic characterization and mechanistic understanding of these interaction products lead us to imidazopyrimidine, glycolyl, and lactolyl moieties. These interaction products have been characterized thoroughly with the use of LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass studies. The study revealed that the reactivity of N-terminal histidine must be considered for formulation development. Moreover, the quality of excipients with respect to presence of impurities must be considered as critical material attributes. Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest. (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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