Physical and biochemical stability of Optison®, an injectable ultrasound contrast agent

Optison® is an ultrasound contrast agent, consisting of gas‐filled microspheres surrounded by a solid shell of heat‐denatured human albumin. Size‐distribution measurements of these microspheres are a critical stability indicating factor, because loss of encapsulated gas eliminates ultrasound contrast activity. Composition of the encapsulated gas is also critical, because air‐filled microspheres do not persist nearly as long in vivo as microspheres filled with less soluble gases. Optison® stability has been tested during exposure to chemical substances expected to dissolve microsphere shells. In addition, size‐distribution and gas‐composition measurements were used to evaluate the effects of external gas composition, elevated temperature, mixing, needle shear and pressure on product stability. Optison® microsphere shells dissolve only when exposed to relatively extreme chemical conditions, such as low pH (