This paper describes the production of a spray dried formulation of Gadovist®, a magnetic resonance imaging (MRI) contrast agent.
Gadovist® is typically administered prior to the performance of an MRI to enhance the visual image by increasing the relaxation signal detected by the scanner. However, it is only available as a 1ml solution for iv administration. For our clients study, a dry powder formulation was desired to enhance the image of the lung. To achieve lung deposition, a particle size of less than 3μm would be required. It was agreed that spray drying would be used to produce a micro-particle of Gadovist® as this offered the opportunity to accurately control the micro-particle size.
The Gadovist ® solution was diluted with ethanol and water and spray dried using a Buchi B-191 fitted with a Schlick 2-fluid nozzle with 0.6mm liquid insert. The ethanol was used to reduce the viscosity of the solution and thereby reduce the particle size. The particles produced were of near uniform size and spherical.
In-vitro characterisation of the micro-particles by laser particle sizing using a SympaTec HELOS gave a volume mean diameter (VMD) of 2.9μm. Analysis of the material using a simple device and a multi-stage liquid impinger demonstrated a mean fine particle dose of 33mg (30-37mg) from a mean delivered dose of 69mg (64-76mg).
The material was subsequently used in an in-vivo MRI study which benefited from the enhanced visual image provided by the contrast agent being deployed to the deep lung region.