Rapid Expansion from Supercritical to Aqueous Solution to Produce Submicron Suspensions of Water‐Insoluble Drugs

Stable suspensions of submicron particles of cyclosporine, a water‐insoluble drug, have been produced by rapid expansion from supercritical to aqueous solution (RESAS). To minimize growth of the cyclosporine particles, which would otherwise occur in the free jet expansion, the solution was sprayed into an aqueous Tween‐80 (Polysorbate‐80) solution. Steric stabilization by the surfactant impedes particle growth and agglomeration. The particles were an order of magnitude smaller than those produced by RESS into air without the surfactant solution. Concentrations as high as 38 mg/mL for 400−700 nm particles were achieved in a 5.0% (w/w) Tween‐80 solution.

[1]  J. Swanson,et al.  Use of microfluidizer processing for preparation of pharmaceutical suspensions , 1996 .

[2]  Valentino J. Stella,et al.  Rapid expansion from supercritical solutions: application to pharmaceutical processes , 1993 .

[3]  A. Randolph,et al.  Precipitation of microsize organic particles from supercritical fluids , 1989 .

[4]  P. Debenedetti,et al.  Solids Formation After the Expansion of Supercritical Mixtures , 1989 .

[5]  G. W. Pace,et al.  Novel injectable formulations of insoluble drugs , 1999 .

[6]  Mark A. McHugh,et al.  Supercritical Fluid Extraction: Principles and Practice , 1986 .

[7]  A. Lele,et al.  Effect of RESS dynamics on polymer morphology , 1994 .

[8]  M. H. Rubinstein,et al.  Praticle Size Reduction in the Ball Mill , 1987 .

[9]  P. Debenedetti.  Supercritical Fluids as Particle Formation Media , 1994 .

[10]  V. Krukonis.  Processing with Supercritical Fluids: Overview and Applications , 1988 .

[11]  김성종,et al.  Microencapsulation , 1974, Springer US.

[12]  E. J. Crosby,et al.  SPRAY DRYING HANDBOOK , 1989 .

[13]  Christopher T. Rhodes,et al.  The spray drying of pharmaceuticals , 1992 .

[14]  D. Tomasko,et al.  Microencapsulation of Naproxen Using Rapid Expansion of Supercritical Solutions , 1996 .

[15]  P. Couvreur,et al.  Polymeric Micro- and Nanoparticles as Drug Carriers , 2001 .

[16]  C. Domingo,et al.  Precipitation of ultrafine organic crystals from the rapid expansion of supercritical solutions over a capillary and a frit nozzle , 1997 .

[17]  K. Johnston,et al.  Formation of poly(1,1,2,2-tetrahydroperfluorodecyl acrylate) submicron fibers and particles from supercritical carbon dioxide solutions , 1995 .

[18]  Jean W. Tom,et al.  Precipitation of poly(l-lactic acid) and composite poly(l-lactic acid)-pyrene particles by rapid expansion of supercritical solutions , 1994 .

[19]  Garnet E. Peck,et al.  The effect of Mill Variables on a Granulation Milling Process , 1990 .

[20]  Ireneo Kikic,et al.  Particle production of steroid drugs using supercritical fluid processing , 1996 .