Back to Search
Start Over
Stable Monomeric Insulin Formulations Enabled by Supramolecular PEGylation of Insulin Analogues
- Source :
- Adv Ther (Weinh), Maikawa, C L, Smith, A A A, Zou, L, Meis, C M, Mann, J L, Webber, M J & Appel, E A 2020, ' Stable Monomeric Insulin Formulations Enabled by Supramolecular PEGylation of Insulin Analogues ', Advanced Therapeutics, vol. 3, no. 1, 1900094 . https://doi.org/10.1002/adtp.201900094
- Publication Year :
- 2020
-
Abstract
- Current "fast-acting" insulin analogues contain amino acid modifications meant to inhibit dimer formation and shift the equilibrium of association states toward the monomeric state. However, the insulin monomer is highly unstable and current formulation techniques require insulin to primarily exist as hexamers to prevent aggregation into inactive and immunogenic amyloids. Insulin formulation excipients have thus been traditionally selected to promote insulin association into the hexameric form to enhance formulation stability. This study exploits a novel excipient for the supramolecular PEGylation of insulin analogues, including aspart and lispro, to enhance the stability and maximize the prevalence of insulin monomers in formulation. Using multiple techniques, it is demonstrated that judicious choice of formulation excipients (tonicity agents and parenteral preservatives) enables insulin analogue formulations with 70-80% monomer and supramolecular PEGylation imbued stability under stressed aging for over 100 h without altering the insulin association state. Comparatively, commercial "fast-acting" formulations contain less than 1% monomer and remain stable for only 10 h under the same stressed aging conditions. This simple and effective formulation approach shows promise for next-generation ultrafast insulin formulations with a short duration of action that can reduce the risk of post-prandial hypoglycemia in the treatment of diabetes.
- Subjects :
- MECHANISM
insulin
medicine.medical_treatment
Supramolecular chemistry
Pharmaceutical Science
Medicine (miscellaneous)
Excipient
AQUEOUS-SOLUTION
Article
THERAPIES
chemistry.chemical_compound
Diabetes mellitus
medicine
Pharmacology (medical)
polymers
TYPE-1
Genetics (clinical)
Pharmacology
chemistry.chemical_classification
diabetes
STABILITY
Chemistry
Insulin
Biochemistry (medical)
PEGylation
RECOGNITION
PEPTIDES
medicine.disease
Combinatorial chemistry
SELF-ASSOCIATION
Amino acid
Monomer
drug delivery
Drug delivery
FIBRILLATION
PRAMLINTIDE
supramolecular
medicine.drug
Subjects
Details
- ISSN :
- 23663987
- Volume :
- 3
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Advanced therapeutics
- Accession number :
- edsair.doi.dedup.....51535dfd08fec299d9d5941f8011b1d3