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

J Control Release. 2005 Nov 2;108(1):21-32. doi: 10.1016/j.jconrel.2005.07.020. Epub 2005 Aug 29.

Abstract

The production and characterization of AI-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 AI-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 (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 mum. Zeta-potential analysis demonstrated that the microparticles would be expected to be stable post-reconstitution. The microparticles retained encapsulated gas post-reconstitution, had high acoustic potency that was stable over time and were physically stable upon exposure to high-power ultrasound, as used clinically. AI-700 has the characteristics desirable for an intravenously administered ultrasound contrast agent for myocardial perfusion echocardiography.

MeSH terms

  • Contrast Media / administration & dosage
  • Contrast Media / chemistry*
  • Drug Compounding / instrumentation
  • Drug Compounding / methods
  • Drug Stability
  • Echocardiography*
  • Excipients
  • Fluorocarbons / administration & dosage
  • Fluorocarbons / chemistry*
  • Injections, Intravenous
  • Lactic Acid / chemistry*
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Porosity

Substances

  • Contrast Media
  • Excipients
  • Fluorocarbons
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • perfluorobutane