Detection of Coronary Artery Disease by Echocardiography using Imagify
     

 
 

Production and Characterization of Imagify

  
 
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 AI-700 were created aseptically by spray drying a water-in-oil emulsion containing polyd, 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 (AI-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 Am. 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. AI-700 has the characteristics desirable for an intravenously administered ultrasound contrast agent for myocardial perfusion echocardiography.
  

Fig. 5 Dual chamber spray dryer

Fig. 6 SEM image of AI-700

Fig. 7 TEM images of the cross-section of AI-700
 
Representative relative acoustic backscatter data at 2.25 MHz are shown in Fig. 8 for AI-700 drug product and Optison. The acoustic backscatter for AI-700 drug product was stable over the 10 min duration of analysis. The acoustic backscatter for Optison dropped dramatically between t =0 and the 2nd analysis point (t =1.25 min). Then A study of stability of the microparticles upon exposure to high-power clinical ultrasound was performed in an attempt to determine a limit for the mechanical index (MI) on a clinical ultrasound machine, above which the microparticles could disintegrate. After imaging for 20 min at an MI of 1.6, changes in particle concentration and particle size for AI-700 were within assay variability. There were no indications of microparticle disintegration.
  

Fig. 8 In vitro acoustic backscatter

AI-700 (triangle) and Optison(square)

Fig. 9 AI-700 microparticle size distribution

a. prior to, and b. post ultrasound imaging for 20 min