Chemical stability of insulin. 3: Influence of excipients, formulation, and pH

摘要: The influence of auxiliary substances and pH on the chemical transformations insulin in pharmaceutical formulation, including various hydrolytic intermolecular cross-linking reactions, was studied. Bacteriostatic agents had a profound stabilizing effect--phenol > m-cresol methylparaben--on deamidation as well reactions. Of isotonicity substances, NaCl generally effect whereas glycerol glucose led to increased deterioration. Phenol sodium chloride exerted their through independent mechanisms. Zinc ions, concentrations that promote association into hexamers, increase stability, higher zinc content no further influence. Protamine gave rise additional formation covalent protamine-insulin products which with increasing protamine concentration. impact excipients processes seems be dictated mainly via an three-dimensional structure. physical state stability also complex, suggesting intricate dependence proximity involved functional groups. At values below five above eight, degrades relatively fast. acid pH, at residue A21 dimerization dominates, disulfide reactions leading polymerization A- B-chains prevailed alkaline medium. Structure-reactivity relationship is proposed main determinant for transformation insulin.