Porous PLGA microparticles: AI-700, an intravenously administered ultrasound contrast agent for use in echocardiography

The production and characterization of Al-700, an intravenously administered ultrasound contrast agent under investigation for myocardial perfusion echocardiography, are described. The product consists of small, porous microparticles filled with decafluorobutane gas, and formulated as a dry powder. Small scale spray drying studies demonstrated that porous PLGA microparticles could be produced with varying porosity using ammonium bicarbonate as a volatile pore-forming agent. The porous microparticles of Al-700 were created aseptically by spray drying a water-in-oil emulsion containing poly-D,L-lactide-co-glycolide, 1,2-diarachidoyl-sn-glycero-3-phosphocholine, and ammonium bicarbonate using a two-chamber spray dryer. The porous microparticles were further formulated into a dry powder drug product (Al-700) containing decafluorobutane gas and excipients. The dry powder was reconstituted with sterile water prior to evaluation. Microscopy demonstrated that the microparticles were sphere-shaped and internally porous. The microparticles were appropriately sized for intravenous administration, having an average diameter of 2.3 mu m. Zeta-potential analysis demonstrated that the microparticles would be expected to be stable post-reconstitution. The microparticles retained encapsulated gas postreconstitution, had high acoustic potency that was stable over time and were physically stable upon exposure to highpower ultrasound, as used clinically. AT-700 has the characteristics desirable for an intravenously administered ultrasound contrast agent for myocardial perfusion echocardiography. (c) 2005 Elsevier B.V All rights reserved.