A novel evaluation of subcutaneous formulations by in vivo magnetic resonance imaging (MRI).
The applicability of magnetic resonance imaging (MRI) for non-invasive in vitro studies of parenteral vehicles without use of marker substances was investigated. A wide range of extended release (ER) formulations such as oils, a lipid emulsion, and water solutions of a cyclodextrin and block co-polymers were visualized in vitro and in vivo by a (1)H-MRI technique. The study included measurements in vitro in a beaker and by injections in pig flesh. In vivo studies were carried out in rats. The contrast of the vehicles vs the background material could be visualized and quantifications of vehicle dispersion and disappearance were performed on obtained in vivo data. A wide range of different vehicles suitable for s.c. ER delivery were tested, such as different oils, a lipid emulsion, and water solutions of a cyclodextrin and block co-polymers. The vehicle volume expansion in vivo was possible to follow. However, this was not generally applicable for all kinds of vehicle component. The tested co-polymers, Poloxamers, were one type of vehicle component that provides an excellent MRI signal. The in vitro tests predicted the suitability of this vehicle for in vivo MRI studies. In the in vivo study of the block co-polymer formulations the apparent vehicle volume increased to a peak value from an initial value close to the injected volume. Thereafter the volume diminished and no vehicle could be detected after 29 h after injection. MRI could be applied for measurements of the dispersion and disappearance of some vehicles at the site of injection after s.c. administration without use of contrast agents.
Madhu
B
B
Wallenberg Laboratory, Bioenergetics Group, Sahlgrenska University Hospital, Göteborg University, SE 413 45 Göteborg, Sweden.
Elmroth
I
I
Lundgren
A
A
Abrahamsson
B
B
Soussi
B
B
D000818:Animals; D003505:Cyclodextrins / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D005079:Excipients; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020442:Poloxamer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D013552:Swine
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D005079:Excipients; D020442:Poloxamer