• English
  • Deutsch
  • Log In
    Password Login
    Research Outputs
    Fundings & Projects
    Researchers
    Institutes
    Statistics
Repository logo
Fraunhofer-Gesellschaft
  1. Home
  2. Fraunhofer-Gesellschaft
  3. Artikel
  4. Predicting drug release and degradation kinetics of long-acting microsphere formulations of tacrolimus for subcutaneous injection
 
  • Details
  • Full
Options
2021
Journal Article
Title

Predicting drug release and degradation kinetics of long-acting microsphere formulations of tacrolimus for subcutaneous injection

Abstract
Today, tacrolimus represents a cornerstone of immunosuppressive therapy for liver and kidney transplants and remains subject of preclinical and clinical investigations, aiming at the development of long-acting depot formulations for subcutaneous injection. One major challenge arises from establishing in vitro-in vivo correlations due to the absence of meaningful in vitro methods predictive for the in vivo situation, together with a strong impact of multiple kinetic processes on the plasma concentration-time profile. In the present approach, two microsphere formulations were compared with regards to their in vitro release and degradation characteristics. A novel biorelevant medium provided the physiological ion and protein background. Release was measured using the dispersion releaser technology under accelerated conditions. A release of 100% of the drug from the carrier was achieved within 7 days. The capability of the in vitro performance assay was verified by the level A in vitro-in vivo correlation analysis. The contributions of in vitro drug release, drug degradation, diffusion rate and lymphatic transport to the absorption process were quantitatively investigated by means of a mechanistic modelling approach. The degradation rate, together with release and diffusion characteristics provides an estimate of the bioavailability and therefore can be a guide to future formulation development.
Author(s)
Gao, G.F.
Ashtikar, M.
Kojima, R.
Yoshida, T.
Kaihara, M.
Tajiri, T.
Shanehsazzadeh, S.
Modh, H.
Wacker, M.G.
Journal
Journal of controlled release  
DOI
10.1016/j.jconrel.2020.11.055
Language
English
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP  
  • Cookie settings
  • Imprint
  • Privacy policy
  • Api
  • Contact
© 2024