Preparation of polymeric microbubbles: formulation studies and product characterisation

Gas filled particles are efficient ultrasound reflectors and are therefore suitable contrast agents for investigations of vital organs such as heart, liver and kidney. In the current study, air filled polymeric microbubbles were made by freeze drying emulsions of a polymer/(-)-camphene solution in a human serum albumin/water phase. An emulsion with low viscosity and a droplet volume median diameter of typically 5-6 mu m, and a relatively narrow droplet size distribution, was produced by high shear homogenisation of the two phases. The emulsion flocculated rapidly and at room temperature, the organic phase solidified. The emulsions were therefore quenched immediately after preparation. Upon freeze drying, (-)-camphene sublimed and the droplets shrunk slightly to form hollow, approximately spherical, microbubbles with volume median diameters of typically 4-5 mu m and well-defined walls, typically 150-200 nm thick. The suspensions from the emulsions with 2.5% w/v polymer in (-)-camphene gave the highest yield of microbubbles when related to the polymer and the most efficient microbubbles. (C) 1997 Elsevier Science B.V.