Patent EA-003665-B1 (EA)
Title: Perforated microparticles and methods of use
Inventor: TARARA THOMAS G
IPC: A61K9/22
Filed: 1998-09-29
Abstract: 1. A method for forming a powder comprising perforated microstructures for pharmaceutical applications by spray drying comprising the steps of: providing a liquid feed stock comprising a bioactive agent, surfactant, and a blowing agent wherein the ratio of blowing agent/surfactant is between 1.0-60 w/w; atomizing said liquid feed stock to produce dispersed droplets; drying said droplets to form perforated microstructures comprising said bioactive agent and surfactant; and collecting said perforated microstructures. 2. The method of claim 1 wherein said blowing agent comprises a fluorinated compound having boiling point greater than about 60 degree C. 3. The method of claim 2 wherein liquid feed stock is emulsion. 4. The method of claim 1 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof. 5. The method of claim 4 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleylphosphatidylcholine, dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine dibehenoylphosphatidylcholine, diarachidoylphosphatidylcholine and combinations thereof. 6. The method of claim 2 wherein said collected perforated microstructures comprise hollow porous microspheres. 7. The method of claim 6 wherein the aerodynamic diameter of said collected perforated microstructures is between 0.5 .mu.m and 5.0 .mu.m. 8. The method of claim 6 wherein geometric diameter of microspheres is less than about 5 .mu.m. 9. The method of claims 2 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, antiinfectives, leukotriene inhibitors or antagonists, antihistamines, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, DNA, viral vectors, antisense agents, proteins, peptides and combinations thereof. 10. The method of claim 2 wherein said ratio of blowing agent/surfactant is greater than 4.8. 11. The method of claim 7 wherein the spray dryer outlet temperature is operated at a temperature at least 20 degree C less than the boiling point of the blowing agent. 12. The method of claim 7 wherein the perforated microstructures comprise geometric diameter of 1-30 mu.m. 13. The method of claim 12 wherein the perforated microstructures comprise geometric diameter of less than about 5 mu.m. 14. The method of claim 12 wherein the perforated microstructures comprise bulk density of less than 0.5 g/cm<3>. 15. The method of claim 12 wherein the perforated microstructures are hollow and porous. 16. The method of claim 12 wherein said perforated microstructures comprise greater than about 20% w/w of a surfactant. 17. The method of claim 12 wherein said liquid feed stock comprises calcium chloride. 18. The method of claim 13 wherein the blowing agent is selected from the group consisting of nitrogen and carbon dioxide. 19. The method of claim 12 wherein the blowing agent comprises a water solubility of less than 10<-3> M. 20. The method of claim 12 wherein the liquid feed stock further comprises a natural or synthetic polymer selected from the group consisting of polylactides, polylactide-glycolides, cyclodextrins, polyacrylates, methylcellulose, carboxymethylcellulose, polyvinyl alcohols, polyanhydrides, polylactams, polyvinyl pyrrolidones, polysaccharides, hyaluronic acid, and proteins. 21. A method for forming a particulate composition for pharmaceutical applications by spray drying comprising: providing a liquid feed stock comprising a phospholipid and calcium chloride; atomizing said feed stock to produce dispersed droplets; drying said droplets in order to form particulates comprising phospholipid and calcium, said particulates comprising a bulk density of less than 0.5 g/cm<3>; and collecting said particulates.