Abstract
Modifying the salt form of active pharmaceutical ingredients is a common method to enhance their physicochemical and biological properties, whilst improving their abiliy to be formulated into medicines that can be effectively delivered to patients. Salts and counterions are especially relevant to peptide therapies given that the majority of low molecular weight peptides synthesised by solid-phase protocols form a trifluoroacetate (TFA) salt due to the use of trifluoroacetic acid in resin cleaving and follow-on purification methods. TFA salts are not viewed as favourably by medicine regulators and can be defined as a new chemical entity entirely due to their different biological and physicochemical properties. Despite some exceptions, the vast majority of therapeutic peptides are marketed as hydrochloride (HCl) or acetate salts, even though most early research and development is centred on TFA salts. The aim of study was to compare the impact of salt form (TFA vs. HCl) on the biostability, cell cytotoxicity, drug release and rheological properties of a Napffky(p)G-OH peptide hydrogel platform that demonstrates promise as a long-acting drug delivery system. This study demonstrated no significant difference between the salt forms for properties important to its intended use. This paper also raises important points for discussion relating to the environmental and regulatory status of peptide salts and their use as pharmaceuticals.
Original language | English |
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Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | Faraday Discussions |
Early online date | 3 Jan 2025 |
DOIs | |
Publication status | Published online - 3 Jan 2025 |
Data Access Statement
Data for this article, including: proteinase K biostability,Oscillatory rheology Napffk(CAB)y(p)G-OH TFA and HCl, MTS
cell cytotoxicity Napffk(CAB)y(p)G-OH TFA and HCl; and in vitro
drug release 28 day CAB release Napffk(CAB)y(p)G-OH TFA and
HCl are available at [Dataset for “Impact of counterion and salt
form on the properties of long-acting injectable peptide
hydrogels for drug delivery”