Porous PLGA microparticles: AI-700, an intravenously administered ultrasound contrast agent for use in echocardiography.
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.
Straub
Julie A
JA
Acusphere, Inc., 500 Arsenal Street, Watertown, MA 02472, USA. julie.straub@acusphere.com
Chickering
Donald E
DE
Church
Charles C
CC
Shah
Bhavdeep
B
Hanlon
Thomas
T
Bernstein
Howard
H
D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D004355:Drug Stability; D004452:Echocardiography; D005079:Excipients; D005466:Fluorocarbons / Q000008:administration & dosage / Q000737:chemistry*; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity
D003287:Contrast Media; D005079:Excipients; D005466:Fluorocarbons; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C108042:perfluorobutane