Investigation of the spatial distribution of injected drugs in tissue using Synchrotron imaging
Novartis AG is a globally active and listed biotechnology and pharmaceutical group headquartered in Basel, Switzerland. The Group's core business is the research, development, production and distribution of prescription medicines. Development in the fields of cardiology, neurology, immunology and oncology focuses on current research results in chemistry and chemical biology as well as on innovative therapies using biotherapeutics and radioligands, RNA-based therapies, gene therapy and cell therapy.
Prefilled syringes (PFS) are primary packaging materials that provide convenience and safety for the subcutaneous injection of parenteral drug solutions. However, an increasingly common problem with the trend towards higher drug concentrations is clogging of the needle during storage due to water loss through evaporation and consequent solidification of the drug. In contrast to all previous studies on this topic, this study focusses on pharmacokinetically relevant aspects and investigates the effects of needle clogging on the spatial distribution of the injected drug in the tissue.
The applied material analytics of ANAXAM using high-resolution Synchrotron CT was used to visualize and analyze the spread pattern and whereabouts of the injected liquid in a pig skin. Studies on a monoclonal antibody solution show that blockages caused by evaporation of water and solidification of the drug solution in the needle tip generally dissolve in the fluid flow during injection. In the initial phase of the injection, the liquid jet only begins to escape from the needle through a narrow channel in the blockage. The resulting high dynamic pressure can alter the distribution of the fluid in the tissue and cause a long tail of fluid that reaches deep into the subcutaneous fiber network. In addition, it has been shown that a plug that has penetrated the tissue would quickly dissolve.
We can only really understand many phenomena through visualisation. Visualising the behaviour of injected drugs in tissue is an important way of understanding the influence a blocked needle can have on the injection, which we have now been able to achieve in this research project. Imaging techniques, especially synchrotron X-ray tomography, made this possible in an impressive way that has never been shown before. 3D images provide even more information and show a really clear model of the injection mechanism. The great expertise of the entire interdisciplinary team made this possible.”
Dr. Alexander Zürn, Associate Director Advanced Testing Global Device & Packaging Development,Novartis
Publication: Does needle clogging change the spatial distribution of injected drug in tissue? New insights by X-ray computed tomography
